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Hereditary ataxia with onset in adulthood v8.28 ISCA-37404-Loss Arina Puzriakova commented on Region: ISCA-37404-Loss: The rating of this gene has been updated to Grey (removed) following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v8.28 JAM2 Ida Ertmanska Added comment: Comment on list classification: There are more than 3 unrelated individuals reported in literature with adult-onset brain calcification and biallelic JAM2 variants, presenting with a cerebellar syndrome (ataxia, dysarthria). Hence, JAM2 should be promoted to Green for Hereditary ataxia with onset in adulthood.
Hereditary ataxia with onset in adulthood v8.27 JAM2 Ida Ertmanska gene: JAM2 was added
gene: JAM2 was added to Hereditary ataxia with onset in adulthood. Sources: Literature
Q1_26_promote_green tags were added to gene: JAM2.
Mode of inheritance for gene: JAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JAM2 were set to 31851307; 32142645
Phenotypes for gene: JAM2 were set to Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824
Review for gene: JAM2 was set to GREEN
Added comment: PMID: 31851307 Cen et al., 2020
Reported 3 unrelated families with primary familial brain calcification. Probands harboured biallelic JAM2 variants: homozygous c.140delT, p.L48Ter; homozygous c.1A>G, p.M1? and compound heterozygous mutations [c.504G>C, p.W168C & c.(67+1_68-1)_(394+1_395-1), p.Y23_V131delinsL]. The clinical phenotypes of the four patients included parkinsonism (3/4), dysarthria (3/4), seizures (1/4), and asymptomatic at the time of report (1 patient at age 37 years); disease onset ages: 20-38 years. 4/4 patients presented with severe calcifications in the cortex in addition to extensive calcifications in multiple brain areas.

PMID: 32142645 Schottlaender et al., 2023
Report of 7 individuals from 4 families with primary familial brain calcification. Detected biallelic JAM2 variants: homozygous c.685C>T, p.Arg229Ter (2 families); comp het c.395−1dupG, c.323G>A & IVS4-1dupG, p.Arg108His; homozygous c.177_180delCAGA, p.Arg60Ter.
Age of onset: childhood (3/7), teenage (2/7), 20s-30s (2/7).
Phenotype: cerebellar syndrome (6/7), Parkinsonism (5/7), dystonia (3/7), cognitive decline (5/6 assessed), brain calcification (7/7).

Functional evidence: JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient’s fibroblasts; human phenotype of brain calcification is replicated in the jam2 complete knockout mouse (jam2 KO).

JAM2 is associated with Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824 (OMIM accesed 16th Mar 2026).
Sources: Literature
Hereditary ataxia with onset in adulthood v8.25 NPTX1 Achchuthan Shanmugasundram commented on gene: NPTX1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v8.25 FAT2 Achchuthan Shanmugasundram commented on gene: FAT2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v8.19 GRID2 Eleanor Williams Mode of pathogenicity for gene: GRID2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v8.18 GRID2 Ida Ertmanska changed review comment from: Comment on list classification: While most reported GRID2-related SCA cases show autosomal recessive inheritance, there are at least 3 unrelated pedigrees described with missense variants in GRID2 M3S2 pore domain, causing dominant / semidominant cerebellar ataxia. One childhood onset case was reported, with a homozygous missense variant in the M3 domain. The heterozygous individuals had first ataxia symptoms in adulthood, which is in the scope of this panel. Hence, the mode of inheritance should be updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal for this panel.; to: Comment on list classification: While most reported GRID2-related SCA cases show autosomal recessive inheritance, there are at least 3 unrelated pedigrees described with missense variants in GRID2 M3S2 pore domain, causing dominant / semidominant cerebellar ataxia. One childhood onset case was reported, with a homozygous missense variant in the M3 domain. The heterozygous individuals had first ataxia symptoms in adulthood, which is in the scope of this panel. Functional evidence in mouse models supports this mechanism of disease. Hence, the mode of inheritance should be updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal for this panel.
Hereditary ataxia with onset in adulthood v8.18 GRID2 Ida Ertmanska commented on gene: GRID2: Comment on list classification: While most reported GRID2-related SCA cases show autosomal recessive inheritance, there are at least 3 unrelated pedigrees described with missense variants in GRID2 M3S2 pore domain, causing dominant / semidominant cerebellar ataxia. One childhood onset case was reported, with a homozygous missense variant in the M3 domain. The heterozygous individuals had first ataxia symptoms in adulthood, which is in the scope of this panel. Hence, the mode of inheritance should be updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal for this panel.
Hereditary ataxia with onset in adulthood v8.16 GRID2 Ida Ertmanska reviewed gene: GRID2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 9285588, 21460832, 25841024, 35882834, 37944084; Phenotypes: Progressive cerebellar ataxia, HP:0002073, Spinocerebellar ataxia, autosomal recessive 18, OMIM:616204; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v8.15 PNPT1 Ida Ertmanska commented on gene: PNPT1: Comment on list classification: There are at least 4 unrelated families with adult-onset Spinocerebellar ataxia and heterozygous PNPT1 variants. While some carriers were very mildly affected or reported unaffected, there is good evidence of PNPT1 variants cosegregating with ataxia, supporting an autosomal dominant inheritance mode. Based on available evidence, this gene should be promoted to Green for Hereditary ataxia with onset in adulthood.
Hereditary ataxia with onset in adulthood v8.15 PNPT1 Ida Ertmanska changed review comment from: PMID: 35411967 Barbier et al., 2022
461–7 French index patient - congenital deafness, ataxia onset at 23yo with a Moderate (24/40) ataxia score - heterozygous for NM_033109.5:c.2091delA; p.Lys697AsnfsTer6 - inherited from an unaffected father.
Australian family A1 - 6 individuals with autosomal dominant progressive ataxia, 3 other individuals were heterozygous and mildly affected.
4 heterozygous candidate variants identified: MSH6 NM_000179.2:c.2633T>C; p.Val878Ala; STON1 NM_001198595.1:c.1231G>A; p.Glu411Lys; PSME4 NM_014614.2:c.3400G>A; p.Glu1134Lys, and PNPT1 NM_033109.5:c.2014-3C>G. Ataxia age of onset = 4 cases under 18 yrs old, 3 adult-onset cases (20-56yrs).

PMID: 39924761 Haddad et al., 2025
Reported two families with heterozygous PNPT1 variants with sensory ataxic neuropathy, including 3 adult-onset cases (20s-30s) - 2 of these cases had no neuropathy score, and 1 case (BII6) with CMT score of 15.
Affected members of Family 1 were heterozygous for NM_033109.5 PNPT1 c.2014‐3C>G; patients in Family 2 were heterozygous for PNPT1 NM_033109.5 c.2143C>T p.Arg715Ter - both variants segregated with disease.

PNPT1 is associated with AD Spinocerebellar ataxia 25 MIM:608703, AR Combined oxidative phosphorylation deficiency 13, MIM:614932, and AR Deafness, autosomal recessive 70, with or without adult-onset neurodegeneration, MIM:614934 in OMIM (accessed 12th Dec 2025).; to: PMID: 35411967 Barbier et al., 2022
461–7 French index patient - congenital deafness, ataxia onset at 23yo with a Moderate (24/40) ataxia score - heterozygous for NM_033109.5:c.2091delA; p.Lys697AsnfsTer6 - inherited from an unaffected father.
Australian family A1 - 6 individuals with autosomal dominant progressive ataxia, 3 other individuals were heterozygous and mildly affected.
4 heterozygous candidate variants identified: MSH6 NM_000179.2:c.2633T>C; p.Val878Ala; STON1 NM_001198595.1:c.1231G>A; p.Glu411Lys; PSME4 NM_014614.2:c.3400G>A; p.Glu1134Lys, and PNPT1 NM_033109.5:c.2014-3C>G. The PNPT1 splice variant introduces a premature stop codon (p.Gln672SerfsTer6) - confirmed by RT-PCR. OXPHOS enzyme activities were normal,
Ataxia age of onset = 4 cases under 18 yrs old, 3 adult-onset cases (20-56yrs).

PMID: 39924761 Haddad et al., 2025
Reported two families with heterozygous PNPT1 variants with sensory ataxic neuropathy, including 3 adult-onset cases (20s-30s) - 2 of these cases had no neuropathy score, and 1 case (BII6) with CMT score of 15.
Affected members of Family 1 were heterozygous for NM_033109.5 PNPT1 c.2014‐3C>G; patients in Family 2 were heterozygous for PNPT1 NM_033109.5 c.2143C>T p.Arg715Ter - both variants segregated with disease.

PNPT1 is associated with AD Spinocerebellar ataxia 25 MIM:608703, AR Combined oxidative phosphorylation deficiency 13, MIM:614932, and AR Deafness, autosomal recessive 70, with or without adult-onset neurodegeneration, MIM:614934 in OMIM (accessed 12th Dec 2025).
Hereditary ataxia with onset in adulthood v8.15 PNPT1 Ida Ertmanska changed review comment from: PMID: 35411967 Barbier et al., 2022
461–7 French index patient - congenital deafness, ataxia onset at 23yo with a Moderate (24/40) ataxia score - heterozygous for NM_033109.5:c.2091delA; p.Lys697AsnfsTer6 - inherited from an unaffected father.
Australian family A1 - 6 individuals with autosomal dominant progressive ataxia, 3 other individuals were heterozygous and mildly affected.
4 heterozygous candidate variants identified: MSH6 NM_000179.2:c.2633T>C; p.Val878Ala; STON1 NM_001198595.1:c.1231G>A; p.Glu411Lys; PSME4 NM_014614.2:c.3400G>A; p.Glu1134Lys, and PNPT1 NM_033109.5:c.2014-3C>G. Ataxia age of onset = 4 cases under 18 yrs old, 3 adult-onset cases (20-56yrs).
The authors pose that heterozygous variants cause lower penetrance and variable expressivity, which may explain later onset and milder phenotype than in homozygous cases.

PMID: 39924761 Haddad et al., 2025
Reported two families with heterozygous PNPT1 variants with sensory ataxic neuropathy, including 3 adult-onset cases (20s-30s).; to: PMID: 35411967 Barbier et al., 2022
461–7 French index patient - congenital deafness, ataxia onset at 23yo with a Moderate (24/40) ataxia score - heterozygous for NM_033109.5:c.2091delA; p.Lys697AsnfsTer6 - inherited from an unaffected father.
Australian family A1 - 6 individuals with autosomal dominant progressive ataxia, 3 other individuals were heterozygous and mildly affected.
4 heterozygous candidate variants identified: MSH6 NM_000179.2:c.2633T>C; p.Val878Ala; STON1 NM_001198595.1:c.1231G>A; p.Glu411Lys; PSME4 NM_014614.2:c.3400G>A; p.Glu1134Lys, and PNPT1 NM_033109.5:c.2014-3C>G. Ataxia age of onset = 4 cases under 18 yrs old, 3 adult-onset cases (20-56yrs).

PMID: 39924761 Haddad et al., 2025
Reported two families with heterozygous PNPT1 variants with sensory ataxic neuropathy, including 3 adult-onset cases (20s-30s) - 2 of these cases had no neuropathy score, and 1 case (BII6) with CMT score of 15.
Affected members of Family 1 were heterozygous for NM_033109.5 PNPT1 c.2014‐3C>G; patients in Family 2 were heterozygous for PNPT1 NM_033109.5 c.2143C>T p.Arg715Ter - both variants segregated with disease.

PNPT1 is associated with AD Spinocerebellar ataxia 25 MIM:608703, AR Combined oxidative phosphorylation deficiency 13, MIM:614932, and AR Deafness, autosomal recessive 70, with or without adult-onset neurodegeneration, MIM:614934 in OMIM (accessed 12th Dec 2025).
Hereditary ataxia with onset in adulthood v8.12 PNPT1 Lucy Jackson gene: PNPT1 was added
gene: PNPT1 was added to Hereditary ataxia with onset in adulthood. Sources: NHS GMS
Mode of inheritance for gene: PNPT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: PNPT1 was set to GREEN
Added comment: Already green on childhood ataxia panel, see https://panelapp.genomicsengland.co.uk/panels/477/gene/PNPT1/
The ataxia phenotype can manifest in adulthood, therefore suggest adding to this panel also.
Sources: NHS GMS
Hereditary ataxia with onset in adulthood v8.12 ISCA-37404-Loss Arina Puzriakova Added comment: Comment on list classification: This region has been deprecated by ClinGen and therefore should be removed from the panel.

This region has been subsumed into ISCA-37478 which is green on multiple GMS panels including this panel (https://panelapp.genomicsengland.co.uk/panels/entities/ISCA-37478-Loss)

Checked and approved by the Genomics England Clinical team.
Hereditary ataxia with onset in adulthood v8.11 PTRH2 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: OMIM phenotype accessed on 24 October 2025.
Hereditary ataxia with onset in adulthood v8.10 EXOSC8 Arina Puzriakova Added comment: Comment on list classification: This gene should be demoted from Green to Red on this panel.

There are currently five reported families with biallelic variants in this gene, all presenting with an infantile-onset disorder (latest reported age of onset is 6 months) (PMIDs: 24989451; 38017281; 34210538). Motor dysfunction is a prominent feature, although it does not overtly manifest as ataxia. Nevertheless, this gene has been added to the 'Ataxia and cerebellar anomalies - narrow panel' due to the presence of cerebellar hypoplasia in affected individuals, and because the early age of onset aligns more closely with that panel.
Hereditary ataxia with onset in adulthood v8.5 RFC1 Lauren Turton Deleted their comment
Hereditary ataxia with onset in adulthood v8.5 RFC1 Lauren Turton changed review comment from: In total 14 patients from 11 unrelated families who have clinically defined CANVAS and are compound heterozygous for a null allele with the (AAGGG)n expansion.
Ronco et al., 2023 PMID: 36289003
7 patients from 5 unrelated families with clinically defined CANVAS with a heterozygous (AAGGG)n expansion in trans with a truncating RFC1 variant. Family 1 and family 4 has two affected siblings.
Weber et al., 2023 PMID: 36478048
2 patients compound heterozygous for null variants with the (AAGGG)n expansion, their phenotypes were characteristic of CANVAS.
Benkirane et al. 2022 PMID: 35883251
2 patients compound heterozygous for null variants and the (AAGGG)n expansion, their phenotypes were characteristic of CANVAS.
Arteche-López et al., 2023 PMID:36250766
2 affected sisters with a nonsense variant and the (AAGGG)n expansion, their phenotypes were characteristic of CANVAS.
King et al., 2022 PMID: 36524104
1 patient with a nonsense variant confirmed in trans with the (AAGGG)n expansion, phenotype characteristic of CANVAS.

Suggest that patients who have been tested for CANVAS, upon analysis of the WGS results if they are known to be heterozygous for (AAGGG)n then analysts should manually check for any LoF RFC1 variants.; to: In total 14 patients from 11 unrelated families who have clinically defined CANVAS and are compound heterozygous for a null allele with the (AAGGG)n expansion.
Ronco et al., 2023 PMID: 36289003
7 patients from 5 unrelated families with clinically defined CANVAS with a heterozygous (AAGGG)n expansion in trans with a truncating RFC1 variant. Family 1 and family 4 has two affected siblings.
Weber et al., 2023 PMID: 36478048
2 patients compound heterozygous for null variants with the (AAGGG)n expansion, their phenotypes were characteristic of CANVAS.
Benkirane et al. 2022 PMID: 35883251
2 patients compound heterozygous for null variants and the (AAGGG)n expansion, their phenotypes were characteristic of CANVAS.
Arteche-López et al., 2023 PMID:36250766
2 affected sisters with a nonsense variant and the (AAGGG)n expansion, their phenotypes were characteristic of CANVAS.
King et al., 2022 PMID: 36524104
1 patient with a nonsense variant confirmed in trans with the (AAGGG)n expansion, phenotype characteristic of CANVAS.

Suggest that patients who have been tested for CANVAS, upon analysis of the WGS results if they are known to be heterozygous for (AAGGG)n then analysts should manually check for any LoF RFC1 variants.
Hereditary ataxia with onset in adulthood v8.5 RAB3A Sarah Leigh changed review comment from: Hengel et al (PMID: 40166812) report six heterozygous RAB3A variants which appear to be associated with a condition that includes cerebellar ataxia; pyramidal features; neurodevelopmental delay. Five of the variants were only seen in one family each, while (NM_002866.5) c.247C>T (p.Arg83Trp) was seen in 14 members from nine families. The age of onset of phenotypic features ranged from 3 months to adulthood. The authors also present supportive functional studies.; to: Hengel et al (PMID: 40166812) report six heterozygous RAB3A variants which appear to be associated with a condition that includes cerebellar ataxia; pyramidal features; neurodevelopmental delay. Five of the variants were only seen in one family each, while (NM_002866.5) c.247C>T (p.Arg83Trp) was seen in 14 members from nine families. The age of onset of phenotypic features ranged from 3 months to adulthood. This gene is appropriate for the Hereditary ataxia with onset in adulthood panel as PMID: 40166812 states "The median age at onset was 26.5 (interquartile range (IQR) 22–32) with gait ataxia as the first symptom in all probands.", In addition, the authors also present supportive functional studies.
Hereditary ataxia with onset in adulthood v8.3 NEU1 Arina Puzriakova Added comment: Comment on list classification: Biallelic variants in the NEU1 gene are associated with Sialidosis (OMIM: 256550). Both Sialidosis Type I (milder, late-onset) and Sialidosis Type II (more severe, early-onset) can present with ataxia as part of a systemic neurological condition.

Overall there are sufficient unrelated cases to warrant inclusion on this panel.
Hereditary ataxia with onset in adulthood v7.23 NPTX1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Jenna Ridley, there are eight unrelated families identified with four different heterozygous missense variants in NPTX1 gene. Seven families were reported with late-onset ataxia, whereas it is early-onset in the six-year-old girl reported in PMID:35560436. There is also functional evidence available for the two variants reported in PMID:34788392.

This gene has been associated with relevant phenotype in OMIM (MIM #620158).

Hence, this gene should be promoted to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Jenna Ridley, there are eight unrelated families identified with four different heterozygous missense variants in NPTX1 gene. Seven families were reported with late-onset ataxia, whereas it is early-onset in the six-year-old girl reported in PMID:35560436. There is also functional evidence available for the two variants reported in PMID:34788392.

This gene has been associated with relevant phenotype in OMIM (MIM #620158).

Hence, this gene should be promoted to green rating in the next GMS update.
Hereditary ataxia with onset in adulthood v7.23 NPTX1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Jenna Ridley, there are eight unrelated families identified with four different missense heterozygous NPTX1 variants. Seven families were reported with late-onset ataxia, whereas it is early onset in the six-year-old girl reported in PMID:35560436. There is also functional evidence available.

This gene has been associated with relevant phenotype in OMIM (MIM #620158).

Hence, this gene should be promoted to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Jenna Ridley, there are eight unrelated families identified with four different heterozygous missense variants in NPTX1 gene. Seven families were reported with late-onset ataxia, whereas it is early-onset in the six-year-old girl reported in PMID:35560436. There is also functional evidence available for the two variants reported in PMID:34788392.

This gene has been associated with relevant phenotype in OMIM (MIM #620158).

Hence, this gene should be promoted to green rating in the next GMS update.
Hereditary ataxia with onset in adulthood v7.23 NPTX1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Jenna Ridley, there are eight unrelated families identified with four different missense heterozygous NPTX1 variants. Seven families were reported with late-onset ataxia, whereas it is early onset in the six-year-old girl reported in PMID:35560436. There is also functional evidence available.

This gene has been associated with relevant phenotype in OMIM (MIM #620158).

Hence, this gene should be promoted to green rating in the next GMS update.
Hereditary ataxia with onset in adulthood v7.22 FAT2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Jenna Ridley, there are four unrelated cases/ families identified with four different heterozygous missense variants in FAT2 gene and reported with late-onset spinocerebellar ataxia. There is some functional work available.

This gene has been associated with relevant phenotype in OMIM (MIM #617769).

This gene should therefore be promoted to green rating in the next GMS update.
Hereditary ataxia with onset in adulthood v7.20 ATXN8OS_CTG Sarah Leigh commented on STR: ATXN8OS_CTG: The numbers of ATXN8OS_CTG required for pathogenicity given by https://stripy.org/database are: 2-37 for normal, 38-79 for intermediate and ≥80 for pathogenic and https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4 gives the repeats as follows: ≤ 50 for normal, 38 - 79 for intermediate and ≥ 71 for pathogenic.
Hereditary ataxia with onset in adulthood v7.20 ATXN8OS_CTG Sarah Leigh STR: ATXN8OS_CTG was added
STR: ATXN8OS_CTG was added to Hereditary ataxia with onset in adulthood. Sources: Literature
STR, NGS Not Validated tags were added to STR: ATXN8OS_CTG.
Mode of inheritance for STR: ATXN8OS_CTG was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for STR: ATXN8OS_CTG were set to 16804541; 10192387
Phenotypes for STR: ATXN8OS_CTG were set to Spinocerebellar ataxia 8, OMIM:608768; spinocerebellar ataxia type 8, MONDO:0012116
Review for STR: ATXN8OS_CTG was set to GREEN
Added comment: ATXN8OS transcribed from the forward strand.

ATXN8OS_CTG is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4

ATXN8OS_CTG is on https://stripy.org/database

ATXN8OS_CTG is on DRAGON 4.02.

The coordinates of the sequence repeats shown above were obtained from DRAGON 4.02, https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4 and https://stripy.org/database were 4:39348424-39348485 (hg38)
The non-pathogenic and pathogenic ranges of the sequence repeats shown above were obtained from: https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Hereditary ataxia with onset in adulthood v7.18 RFC1_AAGGG Sarah Leigh edited their review of STR: RFC1_AAGGG: Added comment: Pathogenicity at the RFC1_AAGGG repeat locus can result from the biallelic replacement of the benign AAAAG repeat with a variable number of AAGGG repeats (PMID: 30926972; 32040566). Furthermore, biallelic expansions of (AAAAG)exp/(AAAGG)exp, (AAAAG)exp/(AAGGG)exp or (AAAGG)exp/(AAGGG)exp were not pathogenic, therefore, it is the biallelic expansions of AAGGG that is pathogenic (PMID: 30926972). An additional pathogenic biallelic expansion :RFC1_ACAGG, was seen in was seen in two Asia-Pacific CANVAS families and a Japanese case (PMID: 33103729, 35355059).; Changed publications to: 30926972, 35883251, 36250766, 36289003, 36524104, 36478048, 32040566, 33103729, 35355059
Hereditary ataxia with onset in adulthood v7.18 RFC1_AAGGG Sarah Leigh STR: RFC1_AAGGG was added
STR: RFC1_AAGGG was added to Hereditary ataxia with onset in adulthood. Sources: Literature
STR, NGS Not Validated tags were added to STR: RFC1_AAGGG.
Mode of inheritance for STR: RFC1_AAGGG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: RFC1_AAGGG were set to 30926972; 35883251; 36250766; 36289003; 36524104; 36478048
Phenotypes for STR: RFC1_AAGGG were set to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, OMIM: 614575
Review for STR: RFC1_AAGGG was set to GREEN
Added comment: RFC1 transcribed from the reverse strand, which means that the repeated sequence is the reverse compliment of the forward strand sequence.

RFC1_AAGGG is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4

RFC1_AAGGG is on https://stripy.org/database

RFC1_AARRG is on DRAGON 4.02.

The coordinates of the sequence repeats shown above were obtained from DRAGON 4.02 and https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4
The coordinates of the sequence repeats from https://stripy.org/database were 4:39348424-39348485 (hg38)
The non-pathogenic and pathogenic ranges of the sequence repeats shown above were obtained from: https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4
And https://stripy.org/database

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Hereditary ataxia with onset in adulthood v7.17 DAB1_ATTTC Sarah Leigh changed review comment from: This is a Nested STR. Pathogenicity is caused by the inclusion of ATTTC repeat (PMID: 29939198; 28686858) within the reference ATTTT repeat. PMID: 28686858 outlined that the pathogenic confirmation of repeats was: [(ATTTT)60–79(ATTTC)31–75(ATTTT)58–90].; to: This is a Nested STR. Pathogenicity is caused by the inclusion of ATTTC repeat (PMID: 29939198; 28686858) within the reference ATTTT repeat. PMID: 28686858 outlined that the pathogenic confirmation of repeats was: [(ATTTT)60–79(ATTTC)31–75(ATTTT)58–90].
Note that DRAGEN 4.02 lists DAB1_ATTTT and not the ATTTC repeat.
Hereditary ataxia with onset in adulthood v7.17 DAB1_ATTTC Sarah Leigh commented on STR: DAB1_ATTTC: This is a Nested STR. Pathogenicity is caused by the inclusion of ATTTC repeat (PMID: 29939198; 28686858) within the reference ATTTT repeat. PMID: 28686858 outlined that the pathogenic confirmation of repeats was: [(ATTTT)60–79(ATTTC)31–75(ATTTT)58–90].
Hereditary ataxia with onset in adulthood v7.17 DAB1_ATTTC Sarah Leigh STR: DAB1_ATTTC was added
STR: DAB1_ATTTC was added to Hereditary ataxia with onset in adulthood. Sources: Literature
STR, NGS Not Validated tags were added to STR: DAB1_ATTTC.
Mode of inheritance for STR: DAB1_ATTTC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for STR: DAB1_ATTTC were set to 29939198; 28686858
Phenotypes for STR: DAB1_ATTTC were set to Spinocerebellar ataxia 37, OMIM: 615945
Review for STR: DAB1_ATTTC was set to GREEN
Added comment: DAB1 is transcribed from the reverse strand, which means that the repeated sequence is the reverse compliment of the forward strand sequence.

DAB1_ATTTC is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4

DAB1_ATTTC is on https://stripy.org/database

DAB1_ATTTT is on DRAGON 4.02.

The coordinates of the sequence repeats shown above were the same on:
https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4 https://stripy.org/database were 8:118366815-118366913 (hg38) and DRAGON 4.02

The non-pathogenic and pathogenic ranges of the sequence repeats shown above were obtained from: https://stripy.org/database

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Hereditary ataxia with onset in adulthood v7.15 NEU1 Lauren Turton gene: NEU1 was added
gene: NEU1 was added to Hereditary ataxia with onset in adulthood. Sources: NHS GMS
Mode of inheritance for gene: NEU1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEU1 were set to 10944856; 11063730; 32752208; 31371146; 30023283
Phenotypes for gene: NEU1 were set to Ataxia; myoclonus
Review for gene: NEU1 was set to GREEN
gene: NEU1 was marked as current diagnostic
Added comment: NEU1-related sialidosis type I is a milder form of the disorder, characterised by visual defects, macular cherry-red spot, myoclonus, ataxia, and seizures. Onset can be variable from childhood to adulthood. Disorder has been well characterised for many years, with several unrelated patients reported.
Sources: NHS GMS
Hereditary ataxia with onset in adulthood v7.15 BEAN1_TGGAA Sarah Leigh commented on STR: BEAN1_TGGAA: The repeat sequence TAAAA in BEAN1 is benign and seen in healthy controls. Although the TAAAA repeat is expanded in patients, it is the TGGAA repeat that is pathogenic repeats. The TGGAA repeat is not seen in healthy controls (PMID: 19878914). A further pathogenic repeat was also seen in two cases [TCAC (TGGAA)exp(TAGAA)exp(TAAAA TAGAA)exp] (PMID: 19878914).
Hereditary ataxia with onset in adulthood v7.15 BEAN1_TGGAA Sarah Leigh commented on STR: BEAN1_TGGAA: BEAN1 transcribed from the forward strand.
BEAN1_TGGAA is on https://gnomad.broadinstitute.org/short-tandem-repeat/SAMD12?dataset=gnomad_r4
BEAN1_TGGAA is on https://stripy.org/database
BEAN1_TGGAA is DRAGON 4.02

The coordinates of the sequence repeats shown above were obtained from https://gnomad.broadinstitute.org/short-tandem-repeat/SAMD12?dataset=gnomad_r4 the coordinates were the same on DRAGON 4.02. The coordinates from https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4 were 16:66490398-66490453 (hg38)

The non-pathogenic and pathogenic ranges of the sequence repeats shown above were obtained from: https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Hereditary ataxia with onset in adulthood v7.15 BEAN1_TGGAA Sarah Leigh STR: BEAN1_TGGAA was added
STR: BEAN1_TGGAA was added to Hereditary ataxia with onset in adulthood. Sources: Literature
NGS Not Validated tags were added to STR: BEAN1_TGGAA.
Mode of inheritance for STR: BEAN1_TGGAA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for STR: BEAN1_TGGAA were set to 19878914
Phenotypes for STR: BEAN1_TGGAA were set to Spinocerebellar ataxia 31, OMIM:117210; spinocerebellar ataxia type 31, MONDO:0007296
Review for STR: BEAN1_TGGAA was set to GREEN
Added comment: Sources: Literature
Hereditary ataxia with onset in adulthood v7.13 SPR Arina Puzriakova Added comment: Comment on mode of inheritance: Sepiapterin reductase deficiency typically follows an autosomal recessive pattern of inheritance. Two cases with different heterozygous variants have been reported (PMID: 29147684, 15241655) although with reduced penetrance in the familial cases and mild form of the disorder in the singleton.

Overall additional evidence is required to conclusively make an association with monoallelic variants and therefore suggesting the MOI is also changed from 'Both mono- and biallelic' to 'Biallelic', with a watchlist_moi tag to monitor for more dominant cases.
Hereditary ataxia with onset in adulthood v7.11 FGF14_TTC Sarah Leigh commented on STR: FGF14_TTC: The name of this STR has been changed from FGF14_GAA to FGF14_TTC as FGF14 is transcribed from the reverse strand of the sequence.
The coordinates for the repeated sequence have been updated to those shown in https://stripy.org/database/FGF14. Previously, the coordinates were for the whole gene, rather than the repeated sequence.
Hereditary ataxia with onset in adulthood v7.10 TUBA4A Sarah Leigh edited their review of gene: TUBA4A: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v7.8 FAT2 Jenna Ridley gene: FAT2 was added
gene: FAT2 was added to Hereditary ataxia with onset in adulthood. Sources: Literature
Mode of inheritance for gene: FAT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FAT2 were set to 29053796; 36339299; 33884300
Phenotypes for gene: FAT2 were set to Spinocerebellar ataxia 45, OMIM:617769
Penetrance for gene: FAT2 were set to Complete
Mode of pathogenicity for gene: FAT2 was set to Other
Review for gene: FAT2 was set to GREEN
Added comment: PMID: 29053796 reported a family (RF14) in which 6 patients spanning 2 generations had late-onset spinocerebellar ataxia after age 40. The proband was noted to have a relatively pure cerebellar syndrome with limb and gait ataxia, downbeat nystagmus, and dysarthria. No detailed clinical information was available for the remaining affected family members. Testing of 5 of the affected individuals was undertaken and c.10758G>C p.(Lys3586Asn) variant was identified in all. Two unaffected members were tested and did not harbour the variant.

An unrelated patient (case DNA056251) had onset of slowly progressive gait and limb ataxia and dysarthria at around 50 years of age. He did not have nystagmus. Brain MRI showed atrophy of the cerebellar vermis and hemosiderin deposits in the mesencephalon. This individual harboured c.10946G>A p.(Ar3649Glu)

PMID: 36339299 reported an 82yo male with a strong f/h of gait imbalance, horizontal gaze evoked nystagmus and ataxic dysarthria. A missense FAT2 variant p.(Met1705Thr) was identified. The variant also detected in his symptomatic surviving brother.

PMID: 33884300 reported 2 siblings with late onset cerebellar ataxia and mild cerebellar atrophy, both with a FAT2 p.(Tyr3636Asp) variant

Only missense variants have been reported.
Sources: Literature
Hereditary ataxia with onset in adulthood v7.8 NPTX1 Jenna Ridley changed review comment from: Eight unrelated families/cases reported with heterozygous missense variants with cerebellar ataxia, oculomotor apraxia, downbeat nystagmus, cognitive impairment reminiscent of cerebellar cognitive affective syndrome, myoclonic tremor and mild cerebellar vermian atrophy on brain imaging.
One of these cases is childhood onset.

PMID:34788392 reported a large multigenerational family with late onset slowly progressive cerebellar ataxia (along with other clinical manifestations) in which 9 members and 6 additional patients from four families harboured c.1165G>A p.(Gly389Arg) variant. Unaffected individuals that were tested did not harbour the variant. An additional patient from another unrelated family harboured c.980A>G p.(Glu327Gly) variant.

PMID:35285082 reported a male patient with slowly progressive late-onset ataxia with c.428G>T p.(Arg143Leu).

PMID: 35288776 report a 58-year-old woman from one of the families reported by Coutelier et al. (2022) (family LUEB01) who presented with oculomotor apraxia at 43 years of age. Her visual disturbances were progressive and severe, with an inability to initiate horizontal saccades or smooth pursuit eye movements. She did not have nystagmus or oculomotor cerebellar signs. Functional MRI studies showed abnormally reduced structural connectivity within the defined oculomotor network of each hemisphere (intrahemispheric dysfunction).

Please note that PMID:35560436 reported a six years old girl with early-onset ataxia with c.1109A>G p.(Gln370Arg)

Only missense variants appear to be reported for this gene.
Sources: Literature; to: Eight unrelated families/cases reported with heterozygous missense variants with cerebellar ataxia, oculomotor apraxia, downbeat nystagmus, cognitive impairment reminiscent of cerebellar cognitive affective syndrome, myoclonic tremor and mild cerebellar vermian atrophy on brain imaging.
One of these cases is childhood onset.

PMID:34788392 reported a large multigenerational family with late onset slowly progressive cerebellar ataxia (along with other clinical manifestations) in which 9 members and 6 additional patients from four families harboured c.1165G>A p.(Gly389Arg) variant. Unaffected individuals that were tested did not harbour the variant. An additional patient from another unrelated family harboured c.980A>G p.(Glu327Gly) variant. Functional work undertaken also support pathogenicity for these variants.

PMID:35285082 reported a male patient with slowly progressive late-onset ataxia with c.428G>T p.(Arg143Leu).

PMID: 35288776 report a 58-year-old woman from one of the families reported by Coutelier et al. (2022) (family LUEB01) who presented with oculomotor apraxia at 43 years of age. Her visual disturbances were progressive and severe, with an inability to initiate horizontal saccades or smooth pursuit eye movements. She did not have nystagmus or oculomotor cerebellar signs. Functional MRI studies showed abnormally reduced structural connectivity within the defined oculomotor network of each hemisphere (intrahemispheric dysfunction).

Please note that PMID:35560436 reported a six years old girl with early-onset ataxia with c.1109A>G p.(Gln370Arg)

Only missense variants appear to be reported for this gene.
Sources: Literature
Hereditary ataxia with onset in adulthood v7.8 NPTX1 Jenna Ridley gene: NPTX1 was added
gene: NPTX1 was added to Hereditary ataxia with onset in adulthood. Sources: Literature
Mode of inheritance for gene: NPTX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NPTX1 were set to 34788392; 35285082; 35288776; 35560436
Phenotypes for gene: NPTX1 were set to Spinocerebellar ataxia 50, OMIM:620158
Penetrance for gene: NPTX1 were set to Complete
Mode of pathogenicity for gene: NPTX1 was set to Other
Review for gene: NPTX1 was set to GREEN
gene: NPTX1 was marked as current diagnostic
Added comment: Eight unrelated families/cases reported with heterozygous missense variants with cerebellar ataxia, oculomotor apraxia, downbeat nystagmus, cognitive impairment reminiscent of cerebellar cognitive affective syndrome, myoclonic tremor and mild cerebellar vermian atrophy on brain imaging.
One of these cases is childhood onset.

PMID:34788392 reported a large multigenerational family with late onset slowly progressive cerebellar ataxia (along with other clinical manifestations) in which 9 members and 6 additional patients from four families harboured c.1165G>A p.(Gly389Arg) variant. Unaffected individuals that were tested did not harbour the variant. An additional patient from another unrelated family harboured c.980A>G p.(Glu327Gly) variant.

PMID:35285082 reported a male patient with slowly progressive late-onset ataxia with c.428G>T p.(Arg143Leu).

PMID: 35288776 report a 58-year-old woman from one of the families reported by Coutelier et al. (2022) (family LUEB01) who presented with oculomotor apraxia at 43 years of age. Her visual disturbances were progressive and severe, with an inability to initiate horizontal saccades or smooth pursuit eye movements. She did not have nystagmus or oculomotor cerebellar signs. Functional MRI studies showed abnormally reduced structural connectivity within the defined oculomotor network of each hemisphere (intrahemispheric dysfunction).

Please note that PMID:35560436 reported a six years old girl with early-onset ataxia with c.1109A>G p.(Gln370Arg)

Only missense variants appear to be reported for this gene.
Sources: Literature
Hereditary ataxia with onset in adulthood v7.6 GDAP2 Sarah Leigh changed review comment from: Biallelic GDAP2 variants have been associated with Spinocerebellar ataxia, autosomal recessive 27 (OMIM:618369), but this gene has not been associated with a phenotype in G2P. At least seven variants have been reported in at least six unrelated cases of OMIM:618369 (PMID: 30084953;32437512;32428220;37070050;38587696).; to: Biallelic GDAP2 variants have been associated with Spinocerebellar ataxia, autosomal recessive 27 (OMIM:618369), but this gene has not been associated with a phenotype in G2P. At least seven variants have been reported in at least six unrelated cases of OMIM:618369 (PMID: 30084953;32437512;32428220;37070050;38587696). The Gdap2 knockdown of Drosophila model resulted in shortened lifespan and motor anomalies that resembled the human phenotype (PMID: 30084953). In vitro expression levels of variants: p.Gln316*, p.His400fs*15 and p.Ser436fs*3 transcripts were reduced in comparison to wild type, resulting in barely detectable levels of variant protein. The transcripts of the remaining variants (p.Thr442fs*7 and
p.Arg253*) tested resulted in truncated proteins (PMID: 32437512).
Hereditary ataxia with onset in adulthood v6.5 TUBA4A Sarah Leigh changed review comment from: At least seven TUBA4A variants have been associated with Amyotrophic lateral sclerosis 22 with or without frontotemporal dementia, (OMIM:616208)(PMID: 25374358; 37418012; 38884572). Spastic ataxia has been noted as an additional phenotypic feature in patients reported by PMID: 37418012;38884572. Furthermore, cultured fibroblasts from 3 patients with different TUBA4A missense variants, showed significant alterations in microtubule organization and dynamics (PMID: 38884572).; to: At least 15 TUBA4A variants have been associated with Amyotrophic lateral sclerosis 22 with or without frontotemporal dementia, (OMIM:616208)(PMID: 25374358; 37418012; 38884572). Spastic ataxia (in 4/13 unrelated cases) and nystagmus (in 5/13 unrelated cases) have been noted as additional phenotypic features in patients reported by PMID: 37418012; 38884572. Furthermore, functional studies show that missense TUBA4A variants significantly alter the microtubule organization and dynamics, diminishing its repolymerization capability (PMID: 25374358; 38884572).
Hereditary ataxia with onset in adulthood v6.1 TUBA4A Nour Elkhateeb gene: TUBA4A was added
gene: TUBA4A was added to Hereditary ataxia with onset in adulthood. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to PMID: 37418012; 38884572
Phenotypes for gene: TUBA4A were set to Ataxia; Spasticity; Nystagmus; Abnormal eye movements; Dysarthria; cognitive decline
Penetrance for gene: TUBA4A were set to unknown
Review for gene: TUBA4A was set to GREEN
Added comment: Heterozygous missense TUBA4A variants (p.Pro173Ser, p.Pro173Arg, and p.Glu415Lys) recently reported to be associated with ataxia and spasticity in 24 individuals from 13 families in PMID: 37418012 and 38884572
Sources: Literature
Hereditary ataxia with onset in adulthood v4.34 ATP2B3 Achchuthan Shanmugasundram changed review comment from: There are six unrelated cases reported with X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood inn three of these cases, while detailed clinical information was not available for the other three cases.; to: There are six unrelated cases reported with X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood in three of these cases, while detailed clinical information was not available for the other three cases.
Hereditary ataxia with onset in adulthood v4.31 ATP2B3 Achchuthan Shanmugasundram commented on gene: ATP2B3: There are six unrelated cases reported with X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood inn three of these cases, while detailed clinical information was not available for the other three cases.
Hereditary ataxia with onset in adulthood v4.31 NAA60 Sarah Leigh commented on gene: NAA60: NAA60 should be green on the Hereditary ataxia with onset in adulthood as four of the families described in table 1 (PMID: 38480682), also displayed either cerebellar syndrome (which often includes ataxia) or cerebellar ataxia (personal communication from Helen Brittain (Genomics England Clinical Fellow).
Hereditary ataxia with onset in adulthood v4.30 MSTO1 Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance should be changed to BIALLELIC, autosomal or pseudoautosomal.
Hereditary ataxia with onset in adulthood v4.26 FGF14_GAA Eleanor Williams commented on STR: FGF14_GAA: After NHS Genomic Medicine Service consideration, the rating of this STR has not been changed and remains Amber.

Comments from review:
Agree that the expansion is likely disease causing. However only a small number of cases have been used to define the number of repeats that could be considered pathogenic. Would recommend that more cases should be identified to better define the pathogenic repeat lengths of this STR. Perhaps study in 100,000 Genomes and GMS data would provide additional cases.

Agree that alleles >250 rpts are of interest and those >300 likely to be diagnostic but concerned that Expansion Hunter will not be able to provide accurate sizing beyond a threshold well below this (~100 repeats). See Supplementary figure S2 of PMID 36493768 for an illustration of this. Can ExpansionHunterDeNovo do better using paired IRRs (PMID PMID: 32345345), or can Expansion Hunter be adapted to factor-in paired IRRs to give a better prediction of expansion size? PCR based assays will also be essential for confirmation and sizing of any repeats detected, not currently available diagnostically to our knowledge.
Hereditary ataxia with onset in adulthood v4.24 SPTAN1 Sarah Leigh changed review comment from: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v4.24 GRN Sarah Leigh changed review comment from: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v4.24 COQ4 Sarah Leigh changed review comment from: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v4.24 SPG7 Sarah Leigh commented on gene: SPG7: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v4.22 RFC1 Sarah Leigh Deleted their comment
Hereditary ataxia with onset in adulthood v4.19 SPTAN1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: Although there are three unrelated cases reported with biallelic SPTAN1 variants and hereditary spastic paraplegia, they do not present with ataxia (PMID:31515523; PMID:34526651). Hence, the MOI should remain as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".
Hereditary ataxia with onset in adulthood v4.17 UCHL1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Hereditary ataxia with onset in adulthood v4.16 UCHL1 Sarah Leigh changed review comment from: In addition to previous reports of Spastic paraplegia 79, autosomal recessive (OMIM:615491), PMID: 35986737 reports a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy in cases with heterozygous UCHL1 variants. The variants included 13 heterozygous loss-of-function variants (15 families) and a heterozygous in-frame insertion (3 families). The affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17), it was also noted in PMID: 35986737 that the condition onset in dominant cases was median 49 years (12-70 years) and in recessive was 7.5 years (2-10 years).; to: In addition to previous reports of Spastic paraplegia 79, autosomal recessive (OMIM:615491), PMID: 35986737 reports a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy in cases with heterozygous UCHL1 variants. The variants included 13 heterozygous loss-of-function variants (15 families) and a heterozygous in-frame insertion (3 families). The affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17), it was also noted in PMID: 35986737 that the condition onset in dominant cases was median 49 years (12-70 years) and in recessive was 7.5 years (2-10 years).
Hereditary ataxia with onset in adulthood v4.15 TDP1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene can now be promoted to AMBER as there are three unrelated cases. The "founder-effect" tag has been added as they are all of Middle Eastern descent and harboured the same homozygous variant. However, the additional patient reported by Ian Berry (Leeds Genetics Laboratory) had the same variant in compound heterozygous state with another novel variant. Hence, this gene can be considered for promotion to GREEN rating at the next major review.; to: Comment on list classification: This gene can now be promoted to AMBER as there are three unrelated cases. The "founder-effect" tag has been added as they are all of Middle Eastern descent and harboured the same homozygous variant. However, the additional patient reported by Ian Berry (Leeds Genetics Laboratory) had the same variant in compound heterozygous state with another novel variant. As there is an additional variant reported, this gene can be considered for promotion to GREEN rating at the next major review.
Hereditary ataxia with onset in adulthood v4.15 TDP1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene can now be promoted to AMBER as there are three unrelated cases. The "founder-effect" tag has been added as they are all of Middle Eastern descent and harboured the same homozygous variant. Hence, it cannot be promoted to green rating.; to: Comment on list classification: This gene can now be promoted to AMBER as there are three unrelated cases. The "founder-effect" tag has been added as they are all of Middle Eastern descent and harboured the same homozygous variant. However, the additional patient reported by Ian Berry (Leeds Genetics Laboratory) had the same variant in compound heterozygous state with another novel variant. Hence, this gene can be considered for promotion to GREEN rating at the next major review.
Hereditary ataxia with onset in adulthood v4.15 PRPS1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: All female cases from the three families were reported with X-linked dominant variants in PRPS1 gene. Hence, the MOI should be changed to "X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)".
Hereditary ataxia with onset in adulthood v4.13 PRPS1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Three families reported with adult-onset ataxia. Although ataxia has been reported in the proband and her mother with X-linked dominant variant in a family in PMID:28967191, it was not reported in the older sister from the family with the same variant. Due to the reduced penetrance in this family, this gene should only be rated amber.; to: Comment on list classification: As reviewed by Zornitza Stark, three families were reported with adult-onset ataxia. Although ataxia has been reported in the proband and her mother with X-linked dominant variant in a family in PMID:28967191, it was not reported in the older sister from the family with the same variant. Due to the reduced penetrance in this family, this gene should only be rated amber.
Hereditary ataxia with onset in adulthood v4.13 PRPS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Three families reported with adult-onset ataxia. Although ataxia has been reported in the proband and her mother with X-linked dominant variant in a family in PMID:28967191, it was not reported in the older sister from the family with the same variant. Due to the reduced penetrance in this family, this gene should only be rated amber.
Hereditary ataxia with onset in adulthood v4.12 FGF14_GAA Eleanor Williams changed review comment from: Comment on list classification: Promoting to amber but there is sufficient evidence to promote to green following GMS review, and configuration in the Rare Disease analysis pipeline.; to: Comment on list classification: Promoting to amber but there is sufficient evidence to promote to green following GMS review, and configuration in the Rare Disease analysis pipeline. GMS expert review is required to confirm that the normal and pathogenic thresholds set are appropriate.
Hereditary ataxia with onset in adulthood v4.11 RFC1 Sarah Leigh commented on gene: RFC1: Five recent papers (PMID: 35883251; 36250766; 36289003; 36524104; 36478048) report nine RFC1 pathogenic variants in trans with the RFC1_AAGGG expansion variant in at least nine unrelated cases. To date such variants have not been detected in the absence of the RFC1_AAGGG, which is why this gene is rated as Red in PanelApp. Detection of the RFC1_AAGGG expansion variant must be validated within the Genomics England pipeline and will be added to PanelApp in due course.
Hereditary ataxia with onset in adulthood v4.6 TDP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

There are a number of functional studies characterising the function of H493R variant in vitro (PMIDs:15920477, 17948061 & 31723605)

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.; to: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

There are a number of functional studies characterising the function of H493R variant in vitro (PMIDs:15920477, 17948061 & 31723605).

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.
Hereditary ataxia with onset in adulthood v4.5 TDP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.; to: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

There are a number of functional studies characterising the function of H493R variant in vitro (PMIDs:15920477, 17948061 & 31723605)

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.
Hereditary ataxia with onset in adulthood v4.5 TDP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene can now be promoted to AMBER as there are three unrelated cases. The "founder-effect" tag has been added as they are all of Middle Eastern descent and harboured the same homozygous variant. Hence, it cannot be promoted to green rating.
Hereditary ataxia with onset in adulthood v3.13 FGF14_GAA Eleanor Williams Added comment: Comment on list classification: Promoting to amber but there is sufficient evidence to promote to green following GMS review, and configuration in the Rare Disease analysis pipeline.
Hereditary ataxia with onset in adulthood v3.12 FGF14_GAA Philip Twiss STR: FGF14_GAA was added
STR: FGF14_GAA was added to Hereditary ataxia - adult onset. Sources: Literature
Mode of inheritance for STR: FGF14_GAA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: FGF14_GAA were set to PMID: 36516086
Phenotypes for STR: FGF14_GAA were set to Late-onset cerebellar ataxia; Episodic features; Nystagmus
Penetrance for STR: FGF14_GAA were set to Complete
Review for STR: FGF14_GAA was set to AMBER
Added comment: New STR disease loci reported to account for significant number of dominant late onset ataxia cases. Not current standard of care therefore no diagnostic accredited PCR assays available currently in UK.
Sources: Literature
Hereditary ataxia with onset in adulthood v3.11 SPTAN1 Achchuthan Shanmugasundram gene: SPTAN1 was added
gene: SPTAN1 was added to Hereditary ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: SPTAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTAN1 were set to 33790315; 35150594; 36331550; 36408834
Phenotypes for gene: SPTAN1 were set to Developmental and epileptic encephalopathy 5, OMIM:613477; Cerebellar ataxia, MONDO:0000437; Hereditary spastic paraplegia, MONDO:0019064
Review for gene: SPTAN1 was set to GREEN
Added comment: Comment on classification: This gene should be rated Green as there are several unrelated cases (many more than three cases identified with different variants) from multiple ethnicities reported with adult-onset ataxia and was also supported by functional studies including results from mouse model.

Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, four unrelated patients displaying p.Lys2083del variant were reported with cerebellar ataxia, of these two had early-onset, one had juvenile-onset and one had adult-onset.

In PMID:36331550, authors carried out SPTAN1 gene enrichment analysis in the rare disease component of the 100,000 Genomes Project and screened 100,000 Genomes Project, DECIPHER database, and GeneMatcher to identify individuals with SPTAN1 variants. Statistically significant enrichment of rare probably damaging SPTAN1 variants were identified in families with hereditary ataxia (HA) or spastic paraplegia (HSP). Out of 31 individuals identified with SPTAN1 variants, five (from three families) were presented with complex HA/HSP and two were presented with pure HA. The two patients presented with pure ataxia had adult-onset.

A 33-year old Korean woman identified with SPTAN1 variant (p.Lys2083del) was reported with cerebellar ataxia in PMID:36408834, being the first reported case of SPTAN1-related cerebellar ataxia.

In addition, a strain of C57BL/6J mice harbouring a single point mutation in Sptan1 (c.3293G > A/ p.Arg1098Gln) with reduced CaM affinity and intrinsically enhanced sensitivity to calpain proteolysis was reported in PMID:33790315. Homozygotes are embryonically lethal and heterozygotes develop a progressive ataxia.
Sources: Literature
Hereditary ataxia with onset in adulthood v3.10 PEX6 Mafalda Gomes commented on gene: PEX6
Hereditary ataxia with onset in adulthood v3.10 NKX2-1 Mafalda Gomes commented on gene: NKX2-1
Hereditary ataxia with onset in adulthood v3.10 CLCN2 Mafalda Gomes commented on gene: CLCN2
Hereditary ataxia with onset in adulthood v3.10 STUB1 Mafalda Gomes commented on gene: STUB1
Hereditary ataxia with onset in adulthood v3.7 UCHL1 Sarah Leigh edited their review of gene: UCHL1: Added comment: In addition to previous reports of Spastic paraplegia 79, autosomal recessive (OMIM:615491), PMID: 35986737 reports a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy in cases with heterozygous UCHL1 variants. The variants included 13 heterozygous loss-of-function variants (15 families) and a heterozygous in-frame insertion (3 families). The affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17), it was also noted in PMID: 35986737 that the condition onset in dominant cases was median 49 years (12-70 years) and in recessive was 7.5 years (2-10 years).; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v3.2 COQ4 Achchuthan Shanmugasundram gene: COQ4 was added
gene: COQ4 was added to Hereditary ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: COQ4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ4 were set to 36047608
Phenotypes for gene: COQ4 were set to Adult-onset ataxia-spasticity spectrum disease; Hereditary spastic paraparesis, MONDO:0019064; Cerebellar ataxia, MONDO:0000437
Review for gene: COQ4 was set to GREEN
Added comment: Comment on classification of this gene: The rating for this gene should be added as GREEN, as this gene has been implicated in adult-onset ataxia, as identified from biallelic variants from three unrelated individuals/ families.

Six patients from four families with bi-allelic variants were reported with adult-Onset ataxia-spasticity spectrum phenotype. Out of these, five patients from three families with bi-allelic variants (c.305G>A & c.473G>A, c.434G>A & c.437T>G, c.202+4A>C & c.202+4A>C) were identified with gait and/or limb ataxia. The severity of the phenotype ranged from mild (c.305G>A & c.473G>A) to more severe (c.202+4A>C & c.202+4A>C ) and the age of onset ranged from 15 to 34 (PMID:36047608).

COQ4 was not associated with adult-onset ataxia-spasticity spectrum disease in OMIM or Gene2Phenotype. However, functional studies performed in patient-derived fibroblasts, yeasts and zebrafish larvae confirms the role of COQ4 in brain development. The coq4 F0 CRISPR zebrafish line particularly showed motor defects and cell reduction in a specific area of the hindbrain, a region reminiscent of the human cerebellum (PMID:33704555).
Sources: Literature
Hereditary ataxia with onset in adulthood v2.168 TERT Arina Puzriakova Added comment: Comment on list classification: This gene should be demoted from Green to Red at the next GMS panel update as there is no link with adult-onset ataxia associated with this gene.

Cerebellar hypoplasia (but without ataxia) has been identified in 2/5 unrelated AR cases to date, who displayed a phenotype of Hoyeraal-Hreidarsson syndrome, a severe variant of DKC (PMIDs: 17785587; 34890115). Furthermore, literature search only revealed a single adult patient (31 years old) who did not present any signs of ataxia (PMID: 18042801).
Hereditary ataxia with onset in adulthood v2.166 GRN Arina Puzriakova changed review comment from: Comment on list classification: This gene should be promoted to Green at the next GMS panel update.; to: Comment on list classification: This gene should be promoted to Green at the next GMS panel update. Multiple cases reported with variable ages of onset but mostly in adulthood. Cerebellar ataxia with cerebellar atrophy on brain MRI is a prominent feature detected in almost all cases with homozygous pathogenic variants in this gene.
Hereditary ataxia with onset in adulthood v2.165 GRM1 Arina Puzriakova Added comment: Comment on mode of inheritance: Should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel review. At least two unrelated cases in literature characterised by AD adult-onset ataxia and supported by functional data, plus additional patients mentioned in Tracy Lester patient cohort.
Hereditary ataxia with onset in adulthood v2.153 PEX6 Sarah Leigh edited their review of gene: PEX6: Added comment: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).; Changed mode of pathogenicity: Other; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v2.153 PEX6 Sarah Leigh Added comment: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
Hereditary ataxia with onset in adulthood v2.149 ABCB7 Eleanor Williams Added comment: Comment on mode of inheritance: Changed the mode of inheritance now this gene has been demoted to amber on this panel and removed the Q3_21_MOI tag.
Hereditary ataxia with onset in adulthood v2.148 ISCA-37478-Gain Eleanor Williams commented on Region: ISCA-37478-Gain
Hereditary ataxia with onset in adulthood v2.148 ISCA-37468-Loss Arina Puzriakova commented on Region: ISCA-37468-Loss
Hereditary ataxia with onset in adulthood v2.148 ISCA-37404-Loss Arina Puzriakova commented on Region: ISCA-37404-Loss
Hereditary ataxia with onset in adulthood v2.148 ISCA-37478-Loss Ivone Leong commented on Region: ISCA-37478-Loss
Hereditary ataxia with onset in adulthood v2.147 HTT_CAG Arina Puzriakova commented on STR: HTT_CAG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
Hereditary ataxia with onset in adulthood v2.147 TBP_CAG Arina Puzriakova commented on STR: TBP_CAG
Hereditary ataxia with onset in adulthood v2.147 PPP2R2B_CAG Arina Puzriakova commented on STR: PPP2R2B_CAG
Hereditary ataxia with onset in adulthood v2.147 NOP56_GGCCTG Arina Puzriakova commented on STR: NOP56_GGCCTG
Hereditary ataxia with onset in adulthood v2.147 FXN_GAA Sarah Leigh commented on STR: FXN_GAA
Hereditary ataxia with onset in adulthood v2.147 CSTB_CCCCGCCCCGCG Sarah Leigh commented on STR: CSTB_CCCCGCCCCGCG
Hereditary ataxia with onset in adulthood v2.147 FMR1_CGG Sarah Leigh commented on STR: FMR1_CGG
Hereditary ataxia with onset in adulthood v2.147 CACNA1A_CAG Eleanor Williams commented on STR: CACNA1A_CAG
Hereditary ataxia with onset in adulthood v2.147 ATXN7_CAG Eleanor Williams commented on STR: ATXN7_CAG
Hereditary ataxia with onset in adulthood v2.147 ATXN3_CAG Eleanor Williams commented on STR: ATXN3_CAG
Hereditary ataxia with onset in adulthood v2.147 ATXN3 Eleanor Williams Deleted their comment
Hereditary ataxia with onset in adulthood v2.147 ATXN3 Eleanor Williams commented on gene: ATXN3
Hereditary ataxia with onset in adulthood v2.147 ATXN2_CAG Ivone Leong commented on STR: ATXN2_CAG
Hereditary ataxia with onset in adulthood v2.147 ATXN10_ATTCT Ivone Leong commented on STR: ATXN10_ATTCT
Hereditary ataxia with onset in adulthood v2.147 ATXN1_CAG Ivone Leong commented on STR: ATXN1_CAG
Hereditary ataxia with onset in adulthood v2.147 ATN1_CAG Ivone Leong commented on STR: ATN1_CAG
Hereditary ataxia with onset in adulthood v2.144 XRCC1 Sarah Leigh commented on gene: XRCC1
Hereditary ataxia with onset in adulthood v2.144 VPS41 Sarah Leigh commented on gene: VPS41
Hereditary ataxia with onset in adulthood v2.144 UCHL1 Sarah Leigh commented on gene: UCHL1
Hereditary ataxia with onset in adulthood v2.144 TSEN15 Sarah Leigh commented on gene: TSEN15
Hereditary ataxia with onset in adulthood v2.144 TBC1D23 Sarah Leigh commented on gene: TBC1D23: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v2.144 SLC9A1 Sarah Leigh commented on gene: SLC9A1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v2.144 SCYL1 Sarah Leigh commented on gene: SCYL1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v2.144 RORA Sarah Leigh commented on gene: RORA: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v2.144 PRICKLE1 Sarah Leigh commented on gene: PRICKLE1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v2.144 MAPK8IP3 Sarah Leigh commented on gene: MAPK8IP3
Hereditary ataxia with onset in adulthood v2.144 ERCC4 Sarah Leigh commented on gene: ERCC4: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v2.144 EBF3 Sarah Leigh commented on gene: EBF3: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v2.144 CLP1 Sarah Leigh commented on gene: CLP1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v2.144 CHMP1A Sarah Leigh commented on gene: CHMP1A: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v2.144 B4GAT1 Sarah Leigh commented on gene: B4GAT1
Hereditary ataxia with onset in adulthood v2.144 AUH Sarah Leigh commented on gene: AUH
Hereditary ataxia with onset in adulthood v2.144 ATP8A2 Sarah Leigh commented on gene: ATP8A2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v2.144 AP1S2 Sarah Leigh commented on gene: AP1S2
Hereditary ataxia with onset in adulthood v2.144 AMPD2 Sarah Leigh commented on gene: AMPD2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v2.144 ADPRHL2 Sarah Leigh commented on gene: ADPRHL2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v2.144 ADGRG1 Sarah Leigh commented on gene: ADGRG1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v2.144 ABCB7 Sarah Leigh commented on gene: ABCB7: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v2.141 TMEM106B Sarah Leigh commented on gene: TMEM106B
Hereditary ataxia with onset in adulthood v2.139 ATP8A2 Sarah Leigh changed review comment from: Zornitza Stark has commented this gene is responsible for a congenital condition and not for an adult onset phenotype. However, table 1 in PMID 31612321 provides a review of the reported variants and their associated clinical features, where a few cases occur after adolescence. This provides some justification for this gene being green on this adult onset panel.
; to: Zornitza Stark has commented this gene is responsible for a congenital condition and not for an adult onset phenotype. Table 1 in PMID 31612321 provides a review of the reported variants and their associated clinical features, although cases are seen after adolescence, where data is available the onset is before 5 years of age. However, the report of a 27 year old male, without age of onset data (PMID: 22892528), provides some justification for this gene being green on this adult onset panel.
Hereditary ataxia with onset in adulthood v2.138 PRDX3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. There is enough evidence to promote this gene to Green at the next GMS panel update.

Rebelo et al., 2021 (PMID: 33889951) reported five simplex families with biallelic variants in PRDX3 leading to complete loss of its encoded protein. Clinical presentation in all individuals predominantly consisted of gait and upper limb ataxia and cerebellar atrophy. Age of onset was at 13, 15, 21, 22 and 23 years of age. Pathogenicity supported by molecular studies using patient fibroblasts, cerebellar medulloblastoma cells and Drosophila.
Hereditary ataxia with onset in adulthood v2.136 MME Arina Puzriakova Publications for gene: MME were set to
Hereditary ataxia with onset in adulthood v2.135 MME Arina Puzriakova Phenotypes for gene: MME were changed from Spinocerebellar ataxia type 43, 617018 to ?Spinocerebellar ataxia 43, OMIM:617018
Hereditary ataxia with onset in adulthood v2.134 RFC1 Eleanor Williams Added comment: Comment on list classification: Changing the rating from amber to red so that it is clear that this gene should not be added to the panel as it is an STR within an intron of this gene that is associated with the neuropathy phenotype.
Hereditary ataxia with onset in adulthood v2.133 RFC1 Dmitrijs Rots changed review comment from: Only STR in this gene is associated with CANVAS / ataxia. Addition of this gene to the panel will result only in unnecessary load of RFC1 SNV/indel/CNV analysis, which are not related to human disorder.; to: Only STR in this gene is associated with CANVAS / ataxia. Addition of this gene to the panel will result only in unnecessary load of RFC1 SNV/indel/CNV analysis, which are not related to human disorder.
Additionallly, RFC1 repeat expansion, is commonly associated with sensory neuropathy (at the moment of presentation usually without clinically prominent ataxia) ,so the STR should be added to the neuropathy panel as well, not just ataxia (PMID: 33969391).
Hereditary ataxia with onset in adulthood v2.133 RFC1 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber, but noting that it is repeat expansions within an intron that is associated with the CANVAS phenotype, not SNVs within the protein coding region. Added to the list of STRs to be added.
Hereditary ataxia with onset in adulthood v2.130 RFC1 Eleanor Williams changed review comment from: The gene is associated with Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) #614575 (AR) with two repeat expansions cited as the allelic variants.

PMID: 30926972 - Cortese et al 2019 - found a recessive intronic AAGGG repeat expansion in the RFC1 gene as a cause of familial CANVAS in 11 families. 4 SNPs around RFC1 were shared by all individuals except in family 5, suggesting a founder haplotype. They found an additional 33 sporadic cases carrying the recessive AAGGG repeat expansion in a cohort of 150 patients diagnosed with sporadic late-onset ataxia (22%). They also note that all sporadic cases with the repeat expansion, except for one individual, shared the same haplotype as familial CANVAS cases. Although the expansion size varied across different families, ranging from around 400 to 2000 repeats, in the majority of cases approximately 1000 repeats were observed. In 304 healthy controls, 4/608 chromosomes (0.7%) chromosomes carried an AAGGG expansion in the heterozygous state. 3 other conformations were observed: (AAAAG)11 (75.5%); (AAAAG)exp(13.0%); and (AAAGG)exp (7.9%). They did not observe a reduced level of RFC1 expression at either the transcript or the protein level in CANVAS patients.

PMID: 31824583 - Akçimen et al 2019 - looked at RFC1 repeat expansions in cohort of Brazilian cases and two cohorts of Canadian cases. 1 Brazilian and 1 Canadian case were found to carry the causative biallelic AAGGG repeat expansion. Two novel repeat sequences were found in the heterozygous state; AAGAG and AGAGG.

PMID: 32851396 - Beecroft et al 2020 - describe a (AAAGG)10-25(AAGGG)exp found in New Zealand Māori and Cook Island Māori individuals which was the cause of CANVAS in all patients. Patients in 2 families also had small number of repeats of the benign variant allele (AAAGG)4-6 at the distal end of the RFC1 pathogenic expansion. The 4 patients with WGS data were found to share the same core haplotype as described in European populations in Cortese et al 2019, plus an additional region.

PMID: 32582864 - Syriani et al 2020 - 29 patients from North America were identified with biallelic repeat expansions in RFC1 (AAGGG) (3.2% of total). Of these 29 patients, 8 (28%) had a clinical diagnosis of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), 14 had cerebellar ataxia with neuropathy (48%), 4 had pure cerebellar ataxia (14%).

PMID: 33969391 - Curro et al 2021 - retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy). Patients previously diagnosed with CANVAS or with a family history of CANVAS were not included. 43 patients (34%) with sensory neuropathy had biallelic AAGGG repeat expansions in RFC1and in none with sensory-motor neuropathy.; to: The gene is associated with Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) #614575 (AR) with two repeat expansions cited as the allelic variants.

There is data to suggest a common haplotype between most cases but this appears to be quite ancient (25000 yo) and so the cases from individuals from different countries can probably be counted as being unrelated. The mechanism of action of this intronic repeat expansion is not yet known.

= AAGGG repeat expansion =

PMID: 30926972 - Cortese et al 2019 - found a recessive intronic AAGGG repeat expansion in the RFC1 gene as a cause of familial CANVAS in 11 families. 4 SNPs around RFC1 were shared by all individuals except in family 5, suggesting a founder haplotype. They found an additional 33 sporadic cases carrying the recessive AAGGG repeat expansion in a cohort of 150 patients diagnosed with sporadic late-onset ataxia (22%). They also note that all sporadic cases with the repeat expansion, except for one individual, shared the same haplotype as familial CANVAS cases. Although the expansion size varied across different families, ranging from around 400 to 2000 repeats, in the majority of cases approximately 1000 repeats were observed. In 304 healthy controls, 4/608 chromosomes (0.7%) chromosomes carried an AAGGG expansion in the heterozygous state. 3 other conformations were observed: (AAAAG)11 (75.5%); (AAAAG)exp(13.0%); and (AAAGG)exp (7.9%). They did not observe a reduced level of RFC1 expression at either the transcript or the protein level in CANVAS patients.

PMID: 31824583 - Akçimen et al 2019 - looked at RFC1 repeat expansions in cohort of Brazilian cases and two cohorts of Canadian cases. 1 Brazilian and 1 Canadian case were found to carry the causative biallelic AAGGG repeat expansion. Two novel repeat sequences were found in the heterozygous state; AAGAG and AGAGG.

PMID: 31230722 - Rafehi et al 2019 - bioinformatics paper looking at using Expansion Hunter de novo on WGS data but also reports RFC1 (AAGGG)exp in 18/22 CANVAS families. Also states that the core ancestral haplotype is estimated to have arisen in Europe more than twenty-five thousand years ago.

PMID: 32851396 - Beecroft et al 2020 - describe a (AAAGG)10-25(AAGGG)exp found in New Zealand Māori and Cook Island Māori individuals which was the cause of CANVAS in all patients. Patients in 2 families also had small number of repeats of the benign variant allele (AAAGG)4-6 at the distal end of the RFC1 pathogenic expansion. The 4 patients with WGS data were found to share the same core haplotype as described in European populations in Cortese et al 2019, plus an additional region.

PMID: 32582864 - Syriani et al 2020 - 29 patients from North America were identified with biallelic repeat expansions in RFC1 (AAGGG) (3.2% of total). Of these 29 patients, 8 (28%) had a clinical diagnosis of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), 14 had cerebellar ataxia with neuropathy (48%), 4 had pure cerebellar ataxia (14%).

PMID: 32694621 - Tsuchiya et al 2020 - found intronic (AAGGG) repeat expansions in RFC1 in 3 (12%) of the familial Japanese patients with CANVAS and 1 (8.5%) of the sporadic ones.

PMID: 33969391 - Curro et al 2021 - retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy). Patients previously diagnosed with CANVAS or with a family history of CANVAS were not included. 43 patients (34%) with sensory neuropathy had biallelic AAGGG repeat expansions in RFC1and in none with sensory-motor neuropathy.

= ACAGG repeat expansion =

PMID: 33103729 - Scriba et al 2020 - report 3 patients with CANVAS from 2 families (2 brothers who reside in Indonesia, but are of Chinese descent, and a isolated female proband from the island nation of Niue) , with a novel, likely pathogenic RFC1 repeat motif (ACAGG)exp. These patients show additional clinical features including fasciculations and elevated creatine kinase levels. They share the core haplotype described in Cortese et al 2019 and Beecroft et al 2020. The RFC1 (ACAGG) motif was found in 7 individuals from 26 745 samples from gnomAD v3; 2 African, 4 South Asian, 1 East Asian.

PMID: 32694621 - Tsuchiya et al 2020 - reports a RFC1 (ACAGG) exp in 1 Japanese individual with sporadic CANVAS.
Hereditary ataxia with onset in adulthood v2.130 MAPK8IP3 Arina Puzriakova Added comment: Comment on list classification: 18 individuals from 17 families reported with de novo variants in this gene (PMIDs: 30612693; 30945334) of which 3 subjects displayed cerebellar atrophy on brain MRI and 2 had ataxia. However, this is a childhood onset condition and literature search did not reveal any evidence of adult onset ataxia associated with this gene. Therefore, MAPK8IP3 should be downgraded from Green here and added to the childhood cerebellar anomalies panel.
Hereditary ataxia with onset in adulthood v2.123 PPP2R2B Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia with onset in adulthood v2.119 TBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia with onset in adulthood v2.117 HTT Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism. Biallelic variants not relevant to this panel.
Hereditary ataxia with onset in adulthood v2.112 ATXN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia with onset in adulthood v2.103 ATXN7 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia with onset in adulthood v2.101 ATXN3 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia with onset in adulthood v2.98 ATXN2 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia with onset in adulthood v2.95 ATXN10 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia with onset in adulthood v2.91 ATN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Hereditary ataxia with onset in adulthood v2.86 CLCN2 Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be changed from 'Both mono- and biallelic' to 'Biallelic' only. Ataxia is a frequent feature of CLCN2-related Leukoencephalopathy (MIM# 615651) which is caused by biallelic variants. Autosomal dominant pathogenic variants are also associated with hyperaldosteronism (MIM# 605635) and susceptibility to idiopathic epilepsy (MIM# 607628) but neither of these phenotypes include ataxia.
Hereditary ataxia with onset in adulthood v2.85 PRPS1 Zornitza Stark gene: PRPS1 was added
gene: PRPS1 was added to Hereditary ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: PRPS1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PRPS1 were set to 33898739; 28967191; 25491489
Phenotypes for gene: PRPS1 were set to Ataxia; deafness; eye disease
Review for gene: PRPS1 was set to AMBER
Added comment: PMID: 25491489:
Heterozygous missense variant, loss of function - PRS enzyme deficiency showed.
Proband and her mother have various degrees of ataxia (examinations at 34yrs and 70yrs, respectively), peripheral neuropathy and hearing loss beyond the ophthalmological symptoms, whereas the phenotype of the affected older sister (36yo) is currently confined to the eye and milder.

PMID: 28967191
in one of the families, heterozygous variants in proband with hearing loss and ataxia developed in the proband in her forties, and ocular manifestations of retinal changes and disc pallor were first confirmed in the two affected daughters in their twenties.

PMID: 33898739:
Heterozygous de novo missense variant in a 30yo female individual, presented with a 5-year history of progressive ataxia. She also had congenital strabismus, infantile-onset hearing loss, and a retinal dystrophy with progressive visual loss for the past 10 years.
Sources: Literature
Hereditary ataxia with onset in adulthood v2.81 PRDX3 Zornitza Stark gene: PRDX3 was added
gene: PRDX3 was added to Hereditary ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: PRDX3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDX3 were set to 33889951
Phenotypes for gene: PRDX3 were set to Cerebellar ataxia (early onset, mild to moderate, progressive)
Review for gene: PRDX3 was set to GREEN
gene: PRDX3 was marked as current diagnostic
Added comment: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex.

Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres.

The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote with a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism.

The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense, suggestive of founder effect.

Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity.

PRDX3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated.

Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species.

In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress.
Sources: Literature
Hereditary ataxia with onset in adulthood v2.80 XRCC1 Arina Puzriakova Added comment: Comment on list classification: This gene will be flagged for GMS review to determine whether there is enough evidence to include XRCC1 on this panel as Green. Only one case with adult onset and the other two with onset in childhood, however inclusion may be justified to ensure identification of edge cases.
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Three individuals from unrelated families all from South Asian descent with cerebellar ataxia and peripheral neuropathy and a recurrent variant (c.1293G>C, 2 homozygotes and a comp het) in the XRCC1 gene. Homozygosity mapping in 2 families confirmed a shared haplotype and the recurrent variant is found in a heterozygous state in an unaffected sib and 4 individuals of South Asian descent in ExAC - indicating that this is a founder variant that is pathogenic when when in trans with a second variant. There is some strong functional evidence that supports pathogenicity, including an animal model that recapitulated human phenotypes such as cerebellar ataxia.
Hereditary ataxia with onset in adulthood v2.72 VPS41 Arina Puzriakova Added comment: Comment on list classification: New gene added by James Polke (North Thames GLH). There are sufficient unrelated families with ataxia (9/11 patients) and VPS41 variants to rate Green - but this appears to be a childhood-onset condition. There is one older subject (22-year-old male - PMID:33764426) for whom the age of onset is not indicated but can probably be inferred by comparison with other cases.

Inclusion may allow for identification of edge cases, but overall VPS41 will be flagged for GMS review to assess whether this is justified.
Hereditary ataxia with onset in adulthood v2.71 VPS41 James Polke gene: VPS41 was added
gene: VPS41 was added to Hereditary ataxia - adult onset. Sources: NHS GMS
Mode of inheritance for gene: VPS41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS41 were set to 32367058; 33875678
Phenotypes for gene: VPS41 were set to Generalised Neurodevelopmental disorder; Ataxia; Dystonia
Review for gene: VPS41 was set to GREEN
Added comment: 32808683: Single individual reported with homozygous canonical splice site variant resulting in exon 7 skipping, and global developmental delay and generalized dystonia. He attained a few words and voluntary limb movements but never sat unsupported. He had pale optic discs and an axonal neuropathy. From 6 years of age, his condition began to deteriorate, with reduced motor abilities and alertness. An MRI of the brain showed atrophy of the superior cerebellar vermis and slimming of the posterior limb of the corpus callosum. VPS41 is component of the HOPS complex and other genes in the complex have been implicated in movement disorders.

PMID 33764426: Additional 9 individuals from 5 unrelated families reported.
Sources: NHS GMS
Hereditary ataxia with onset in adulthood v2.71 TBC1D23 Sarah Leigh commented on gene: TBC1D23
Hereditary ataxia with onset in adulthood v2.70 SLC9A1 Sarah Leigh commented on gene: SLC9A1
Hereditary ataxia with onset in adulthood v2.67 SCYL1 Sarah Leigh commented on gene: SCYL1
Hereditary ataxia with onset in adulthood v2.66 RORA Sarah Leigh commented on gene: RORA
Hereditary ataxia with onset in adulthood v2.62 PRICKLE1 Sarah Leigh commented on gene: PRICKLE1
Hereditary ataxia with onset in adulthood v2.61 AMPD2 Sarah Leigh Added comment: Comment on phenotypes: Spastic paraplegia 63 OMIM:615686 from homozygous frameshift reported in single family (Novarino et al, 2014).
Hereditary ataxia with onset in adulthood v2.60 AMPD2 Sarah Leigh commented on gene: AMPD2
Hereditary ataxia with onset in adulthood v2.59 ADGRG1 Sarah Leigh commented on gene: ADGRG1
Hereditary ataxia with onset in adulthood v2.59 ABCB7 Sarah Leigh commented on gene: ABCB7
Hereditary ataxia with onset in adulthood v2.57 EBF3 Sarah Leigh changed review comment from: GMS review is requested in regard to Zornitza Stark's review; that the phenotype associated with EBF3 - Hypotonia, ataxia, and delayed development syndrome OMIM:617330 is not relevant to this panel as it is not an adult onset condtion.; to: The tag Q2_21_phenotype has been added to this gene, because variants in this gene are associated with childhood onset of ataxia in Hypotonia, ataxia, and delayed development syndrome OMIM:617330.
Hereditary ataxia with onset in adulthood v2.57 ERCC4 Sarah Leigh commented on gene: ERCC4: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least nine variants reported in at least seven cases of Xeroderma pigmentosum, group F OMIM:278760, where neurodegeneration and ataxia was present (PMID 29403087; 28431612; 29892709).
Hereditary ataxia with onset in adulthood v2.56 ERCC4 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Hereditary ataxia with onset in adulthood v2.52 ATP8A2 Sarah Leigh changed review comment from: Zornitza Stark has commented this gene is responsible for a congenital condition and not for an adult onset phenotype. However, table 1 in PMID 31612321 provides a review of the reported variants and their associated clinical features, where a few cases occur after adolescence. This provides justification for this gene being green on this adult onset panel.; to: Zornitza Stark has commented this gene is responsible for a congenital condition and not for an adult onset phenotype. However, table 1 in PMID 31612321 provides a review of the reported variants and their associated clinical features, where a few cases occur after adolescence. This provides some justification for this gene being green on this adult onset panel.
Hereditary ataxia with onset in adulthood v2.50 TSEN15 Arina Puzriakova Added comment: Comment on list classification: This gene should be demoted from Green to Red at the next GMS panel review
Hereditary ataxia with onset in adulthood v2.44 UCHL1 Arina Puzriakova changed review comment from: Tagged for GMS expert review (Q2_21) to seek opinion on whether this gene rating needs to be changed. Ten individuals from four families have been reported with a childhood-onset neurodegenerative disorder and different biallelic variants in this gene. Age of onset ranges from 2 to 10 years, however visual loss appears to be one of the first presenting features in most cases and ataxia becomes apparent later in the clinical course (PMIDs: 23359680; 28007905; 29735986; 32656641); to: Tagged for GMS expert review (Q2_21) to seek opinion on whether this gene rating needs to be changed. Ten individuals from four families have been reported with a childhood-onset neurodegenerative disorder and different biallelic variants in this gene. Age of onset ranges from 2 to 10 years, however visual loss appears to be one of the first presenting features in most cases and ataxia becomes apparent later in the clinical course (PMIDs: 23359680; 28007905; 29735986; 32656641). Inclusion may be justified to ensure that edge cases may be identified.
Hereditary ataxia with onset in adulthood v2.42 ADPRHL2 Sarah Leigh changed review comment from: The Q2_21_expert_review tag has been added to this gene as there is a conflict of opinion of the rating of ADPRHL2 on the this - Hereditary ataxia - adult onset - panel, as variants in ADPRHL2 are usually associated with Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170 in infancy or in childhood. The green rating may be justifyied inorder to ensure that edge cases may be identified.
GMS opinion is sort on this issue.; to: The Q2_21_expert_review tag has been added to this gene as there is a conflict of opinion of the rating of ADPRHL2 on the this - Hereditary ataxia - adult onset - panel, as variants in ADPRHL2 are usually associated with Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170 in infancy or in childhood. The green rating may be justified to ensure that edge cases may be identified.
GMS opinion is sort on this issue.
Hereditary ataxia with onset in adulthood v2.42 ADPRHL2 Sarah Leigh changed review comment from: The Q2_21_expert_review has been added to this gene as there is a conflict of opinion of the rating of this ADPRHL2 on the this - Hereditary ataxia - adult onset - panel, as variants in ADPRHL2 are usually associated with Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170 in infancy or in childhood.
GMS opinion is sort on this issue.; to: The Q2_21_expert_review tag has been added to this gene as there is a conflict of opinion of the rating of ADPRHL2 on the this - Hereditary ataxia - adult onset - panel, as variants in ADPRHL2 are usually associated with Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170 in infancy or in childhood. The green rating may be justifyied inorder to ensure that edge cases may be identified.
GMS opinion is sort on this issue.
Hereditary ataxia with onset in adulthood v2.42 ADPRHL2 Sarah Leigh changed review comment from: The Q2_21_expert_review has been added to this gene as there is a conflict of opinion of the rating of this ADPRHL2 on the this - Hereditary ataxia - adult onset - panel.as variants in ADPRHL2 are usually associated with Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170 in infancy or in childhood.
GMS opinion is sort on this issue.; to: The Q2_21_expert_review has been added to this gene as there is a conflict of opinion of the rating of this ADPRHL2 on the this - Hereditary ataxia - adult onset - panel, as variants in ADPRHL2 are usually associated with Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170 in infancy or in childhood.
GMS opinion is sort on this issue.
Hereditary ataxia with onset in adulthood v2.42 EEF2 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber on advice of Genomics England clinical team. Amber rating selected pending further cases and delineation of the phenotype
Hereditary ataxia with onset in adulthood v2.41 EEF2 Eleanor Williams gene: EEF2 was added
gene: EEF2 was added to Hereditary ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: EEF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EEF2 were set to 23001565; 33355653
Phenotypes for gene: EEF2 were set to Spinocerebellar ataxia 26 OMIM:609306
Review for gene: EEF2 was set to AMBER
Added comment: Provisionally associated with ?Spinocerebellar ataxia 26 #609306 (AD) in OMIM based on Hekman et al 2012 case.

PMID: 23001565 - Hekman et al 2012 - report a six-generation kindred of Norwegian ancestry with a late-onset pure cerebellar ataxia in which a heterozygous P596H substitution in eEF2 was found to segregate with the disease phenotype in 24 individuals and two currently asymptomatic individuals. Functional studies in yeast showed that the variant (P580H in the EFT2 gene in yeast) affected translational fidelity.

PMID: 33355653 - Nabais Sá et al 2021 - identified de novo EEF2 missense variants in 3 unrelated children (3, 6 and 9 years of age) with a mild phenotype comprising motor delay and relative macrocephaly associated with ventriculomegaly.
Sources: Literature
Hereditary ataxia with onset in adulthood v2.23 CLP1 Sarah Leigh changed review comment from: Zornitza Stark has reviewed this gene as red on this panel, as the phenotype associated with variants in CLP1 is evident in childhood. Furthermore, only a single Founder variant has been reported, in patients.; to: Zornitza Stark has reviewed this gene as red on this panel, as the phenotype associated with variants in CLP1 is evident in childhood. Furthermore, only a single (founder) variant has been reported, in patients.
Hereditary ataxia with onset in adulthood v2.17 RFC1 Zornitza Stark edited their review of gene: RFC1: Added comment: A novel RFC1 repeat motif (ACAGG) in two Asia-Pacific CANVAS families reported in PMID 33103729. Both of these need to be added as STRs but I haven't quite figured out how to do it!; Changed publications: 30926972, 33103729
Hereditary ataxia with onset in adulthood v2.16 TMEM106B Arina Puzriakova Added comment: Comment on list classification: This gene has been flagged for review at the next GMS panel update (added 'for-review tag) as there is only enough evidence for TMEM106B to be rated AMBER on this panel.

Only 2/6 cases present ataxia, which is mild in one individual. Cases are more likely to be recognised for the leukodystrophy feature of this disease presentation; however, this could be reviewed if evidence emerges of a more prominent ataxic phenotype.
Hereditary ataxia with onset in adulthood v2.15 TMEM106B Arina Puzriakova reviewed gene: TMEM106B: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 29186371, 29444210, 30643851, 32595021; Phenotypes: Leukodystrophy, hypomyelinating, 16 OMIM:617964; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary ataxia with onset in adulthood v2.12 HTT_CAG Arina Puzriakova Added comment: Comment on list classification: This STR has been removed at the request of GHLs for the GMS Neurology Specialist Test Group as it is available as a core test for R68 Huntington Disease. Inclusion on panels for other neurological CIs raises concerns regarding counselling, and so it has been agreed that HTT_CAG will be excluded from this panel.
Hereditary ataxia with onset in adulthood v2.10 FMR1_CGG Arina Puzriakova STR: FMR1_CGG was added
STR: FMR1_CGG was added to Hereditary ataxia - adult onset. Sources: Expert list
STR tags were added to STR: FMR1_CGG.
Mode of inheritance for STR: FMR1_CGG was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for STR: FMR1_CGG were set to Fragile X syndrome, 300624
Review for STR: FMR1_CGG was set to GREEN
Added comment: New STR submitted and discussed with GLHs for the GMS Neurology Specialist Test Group, who agreed that there is sufficient evidence to rate this STR Green on this panel.
Sources: Expert list
Hereditary ataxia with onset in adulthood v2.9 ERCC4 Zornitza Stark gene: ERCC4 was added
gene: ERCC4 was added to Hereditary ataxia - adult onset. Sources: Expert list
Mode of inheritance for gene: ERCC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC4 were set to 29403087; 28431612; 29892709
Phenotypes for gene: ERCC4 were set to Cerebellar ataxia; Xeroderma pigmentosum, group F, MIM# 278760
Review for gene: ERCC4 was set to GREEN
gene: ERCC4 was marked as current diagnostic
Added comment: Bi-allelic variants in ERCC4 cause a range of phenotypes, including xeroderma pigmentosum complementation group F (XP-F), Cockayne syndrome, and Fanconi anaemia. Seven unrelated individuals reported with slowly progressive cerebellar ataxia and cognitive decline with choreiform involuntary movement, with onset in adolescence/adulthood. Brain MRIs demonstrated atrophy that included the cerebellum and brainstem. Of note, cutaneous symptoms were very mild in 5/7: there was normal to very mild pigmentation of exposed skin areas and/or an equivocal history of pathological sunburn.
Sources: Expert list
Hereditary ataxia with onset in adulthood v2.8 ATXN8 Eleanor Williams commented on gene: ATXN8
Hereditary ataxia with onset in adulthood v2.8 RFC1 Zornitza Stark gene: RFC1 was added
gene: RFC1 was added to Hereditary ataxia - adult onset. Sources: Expert Review
Mode of inheritance for gene: RFC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFC1 were set to 30926972
Phenotypes for gene: RFC1 were set to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome OMIM 614575
Mode of pathogenicity for gene: RFC1 was set to Other
Review for gene: RFC1 was set to GREEN
gene: RFC1 was marked as current diagnostic
Added comment: 23 affected individuals from 11 families reported with biallelic AAGGG repeat expansion in intron 2. Expansion carrier frequency of 0.7% in Europeans.
Sources: Expert Review
Hereditary ataxia with onset in adulthood v2.0 ADPRHL2 Louise Daugherty commented on gene: ADPRHL2: Added new-gene-name tag, new approved HGNC gene symbol for ADPRHL2 is ADPRS
Hereditary ataxia with onset in adulthood v1.210 HTT Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red
Hereditary ataxia with onset in adulthood v1.209 DYNC1H1 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Hereditary ataxia with onset in adulthood v1.208 DYNC1H1 Louise Daugherty Mode of pathogenicity for gene: DYNC1H1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v1.206 COG5 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019 : The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.205 COG5 Louise Daugherty Added comment: Comment on mode of inheritance: changed MOI from external expert review
Hereditary ataxia with onset in adulthood v1.204 CAPN1 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019 : The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.203 VRK1 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Hereditary ataxia with onset in adulthood v1.202 PNKD Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019 : The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.201 KCNQ3 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Hereditary ataxia with onset in adulthood v1.200 KCNQ3 Louise Daugherty Mode of pathogenicity for gene: KCNQ3 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v1.199 SLC6A5 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red
Hereditary ataxia with onset in adulthood v1.198 PAX6 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red
Hereditary ataxia with onset in adulthood v1.196 AARS Louise Daugherty commented on gene: AARS: Added new-gene-name tag, new approved HGNC gene symbol for AARS is AARS1
Hereditary ataxia with onset in adulthood v1.195 POLG2 Sarah Leigh Added comment: Comment on mode of inheritance: Reporting and characterization of a homozygous POLG2 variant in mitochondrial DNA depletion syndrome and in an autosomal recessive epilepsy family without ophthalmoplegia (PMID 27592148; 30157269; 31286721).
Hereditary ataxia with onset in adulthood v1.194 TBP_CAG Louise Daugherty commented on STR: TBP_CAG: Discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this STR Green
Hereditary ataxia with onset in adulthood v1.194 PPP2R2B_CAG Louise Daugherty commented on STR: PPP2R2B_CAG: Discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this STR Green
Hereditary ataxia with onset in adulthood v1.194 NOP56_GGCCTG Louise Daugherty commented on STR: NOP56_GGCCTG: Discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this STR Green
Hereditary ataxia with onset in adulthood v1.194 HTT_CAG Louise Daugherty commented on STR: HTT_CAG: Discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this STR Green
Hereditary ataxia with onset in adulthood v1.194 FXN_GAA Louise Daugherty commented on STR: FXN_GAA: Discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this STR Green
Hereditary ataxia with onset in adulthood v1.194 ATXN7_CAG Louise Daugherty commented on STR: ATXN7_CAG: Discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this STR Green
Hereditary ataxia with onset in adulthood v1.194 ATXN3_CAG Louise Daugherty commented on STR: ATXN3_CAG: Discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this STR Green
Hereditary ataxia with onset in adulthood v1.194 ATXN2_CAG Louise Daugherty commented on STR: ATXN2_CAG: Discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this STR Green
Hereditary ataxia with onset in adulthood v1.194 ATXN1_CAG Louise Daugherty commented on STR: ATXN1_CAG: Discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this STR Green
Hereditary ataxia with onset in adulthood v1.194 ATXN10_ATTCT Louise Daugherty commented on STR: ATXN10_ATTCT: Discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this STR Green
Hereditary ataxia with onset in adulthood v1.194 ATN1_CAG Louise Daugherty commented on STR: ATN1_CAG: Discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this STR Green
Hereditary ataxia with onset in adulthood v1.194 ISCA-37478-Gain Louise Daugherty commented on Region: ISCA-37478-Gain: Discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this CNV Green
Hereditary ataxia with onset in adulthood v1.194 ISCA-37404-Loss Louise Daugherty commented on Region: ISCA-37404-Loss: Discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this CNV Green
Hereditary ataxia with onset in adulthood v1.189 OPA3 Louise Daugherty changed review comment from: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green; to: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green. Confirmed MOI should be AR (Biallelic)
Hereditary ataxia with onset in adulthood v1.188 DAB1 Louise Daugherty edited their review of gene: DAB1: Added comment: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red; Changed rating: AMBER
Hereditary ataxia with onset in adulthood v1.188 BEAN1 Louise Daugherty commented on gene: BEAN1: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red
Hereditary ataxia with onset in adulthood v1.188 AARS Louise Daugherty commented on gene: AARS: Upgraded rating from Red to Amber. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Hereditary ataxia with onset in adulthood v1.188 XRCC1 Louise Daugherty commented on gene: XRCC1: Added watchlist tag. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Hereditary ataxia with onset in adulthood v1.188 VAMP1 Louise Daugherty commented on gene: VAMP1: Added watchlist tag. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Hereditary ataxia with onset in adulthood v1.188 TGM6 Louise Daugherty commented on gene: TGM6: Downgraded rating from Amber to Red. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red
Hereditary ataxia with onset in adulthood v1.188 SLC9A1 Louise Daugherty commented on gene: SLC9A1: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.188 POLG2 Louise Daugherty commented on gene: POLG2: Downgraded rating from Amber to Red. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red
Hereditary ataxia with onset in adulthood v1.188 PDYN Louise Daugherty commented on gene: PDYN: Downgraded rating from Amber to Red. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red
Hereditary ataxia with onset in adulthood v1.188 CACNB4 Louise Daugherty commented on gene: CACNB4: Downgraded rating from Amber to Red. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red
Hereditary ataxia with onset in adulthood v1.188 ATXN8 Louise Daugherty edited their review of gene: ATXN8: Added comment: Downgraded rating from Amber to Red. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red; Changed rating: AMBER
Hereditary ataxia with onset in adulthood v1.188 RELN Louise Daugherty commented on gene: RELN: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red
Hereditary ataxia with onset in adulthood v1.188 ZFYVE26 Louise Daugherty commented on gene: ZFYVE26: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.188 TPP1 Louise Daugherty commented on gene: TPP1: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.188 PRRT2 Louise Daugherty commented on gene: PRRT2: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.188 NHLRC1 Louise Daugherty commented on gene: NHLRC1: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.188 MRE11 Louise Daugherty commented on gene: MRE11: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.188 MARS2 Louise Daugherty commented on gene: MARS2: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.188 FMR1 Louise Daugherty commented on gene: FMR1: Downgraded Green to Red. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red
Hereditary ataxia with onset in adulthood v1.188 DNAJC5 Louise Daugherty commented on gene: DNAJC5: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.188 ATP1A2 Louise Daugherty commented on gene: ATP1A2: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.188 TTC19 Louise Daugherty commented on gene: TTC19: Downgraded Green to Red. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red
Hereditary ataxia with onset in adulthood v1.188 TINF2 Louise Daugherty commented on gene: TINF2: Downgraded Green to Red. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red
Hereditary ataxia with onset in adulthood v1.188 SLC25A46 Louise Daugherty commented on gene: SLC25A46: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.188 SAR1B Louise Daugherty commented on gene: SAR1B: Downgraded Green to Amber. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Hereditary ataxia with onset in adulthood v1.188 OPA3 Louise Daugherty commented on gene: OPA3: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.188 MORC2 Louise Daugherty commented on gene: MORC2: Downgraded rating from Green to Amber, Green gene for childhood onset. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Hereditary ataxia with onset in adulthood v1.188 MFN2 Louise Daugherty commented on gene: MFN2: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.188 GDAP2 Louise Daugherty commented on gene: GDAP2: Downgraded rating from Green to Amber. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Hereditary ataxia with onset in adulthood v1.188 EPM2A Louise Daugherty commented on gene: EPM2A: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.188 ELOVL5 Louise Daugherty commented on gene: ELOVL5: Downgraded rating from Green to Amber. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Hereditary ataxia with onset in adulthood v1.188 ARSA Louise Daugherty commented on gene: ARSA: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Hereditary ataxia with onset in adulthood v1.186 CACNA1A_CAG Louise Daugherty commented on STR: CACNA1A_CAG: STR missing from original lists submitted by the GLHs from GMS Neurology Specialist Test Group. Discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this STR Green
Hereditary ataxia with onset in adulthood v1.186 CSTB_CCCCGCCCCGCG Louise Daugherty Added comment: Comment on list classification: STR missing from original lists submitted by the GLHs from GMS Neurology Specialist Test Group. Discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this STR Green
Hereditary ataxia with onset in adulthood v1.183 ISCA-37478-Loss Louise Daugherty commented on Region: ISCA-37478-Loss: CNV missing from original lists submitted by the GLHs from GMS Neurology Specialist Test Group. Discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this CNV Green
Hereditary ataxia with onset in adulthood v1.183 ISCA-37468-Loss Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this CNV Red
Hereditary ataxia with onset in adulthood v1.182 TUBB2A Louise Daugherty commented on gene: TUBB2A: No discrepancy - this gene should remain Red even though Amber review - see comment from Wessex and West Midlands GLH
Hereditary ataxia with onset in adulthood v1.182 TUBB Louise Daugherty commented on gene: TUBB: No discrepancy - this gene should remain Red even though Amber review - see comment from Wessex and West Midlands GLH
Hereditary ataxia with onset in adulthood v1.181 GALC Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: New gene and Green rating added to panel by Nick Beauchamp (Sheffield Diagnostic Genetics Service) on behalf of YNEGLH. The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Hereditary ataxia with onset in adulthood v1.179 PEX2 Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: New gene and Green rating added to panel by Nick Beauchamp (Sheffield Diagnostic Genetics Service) on behalf of YNEGLH. The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Hereditary ataxia with onset in adulthood v1.178 GALC Nick Beauchamp gene: GALC was added
gene: GALC was added to Hereditary ataxia - adult onset. Sources: Expert Review
Mode of inheritance for gene: GALC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALC were set to 26915362, 20886637
Phenotypes for gene: GALC were set to KRABBE DISEASE, 245200
Review for gene: GALC was set to GREEN
gene: GALC was marked as current diagnostic
Added comment: Unusual presentation but 5 member kindred presenting with predominant cerebellar ataxia (26915362) and two patients with spastic ataxia reported by Tappino et al 2010 (20886637). Further case report with patient developing progressive ataxia (doi: 10.5455/ijmsph.2014.150320141)
Sources: Expert Review
Hereditary ataxia with onset in adulthood v1.178 PEX2 Nick Beauchamp gene: PEX2 was added
gene: PEX2 was added to Hereditary ataxia - adult onset. Sources: Expert Review
Mode of inheritance for gene: PEX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX2 were set to 23430938; 7931872; 21392394
Phenotypes for gene: PEX2 were set to PEROXISOME BIOGENESIS DISORDER 5B,614867
Review for gene: PEX2 was set to GREEN
gene: PEX2 was marked as current diagnostic
Added comment: Three patients with PEX2 mutations either compound het or homozygous. Mild symptoms that included no cognitive impairment but does show gait ataxia, dysarthria, dysmetria, areflexia, and bilateral pes cavus.
Sources: Expert Review
Hereditary ataxia with onset in adulthood v1.177 ATXN7_CAG Louise Daugherty changed review comment from: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group; to: Green rating for STR submitted on behalf of James Polke, on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.177 ATXN3_CAG Louise Daugherty changed review comment from: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group; to: Green rating for STR submitted on behalf of James Polke, on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.174 NOP56 Louise Daugherty changed review comment from: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group; to: Review and rating submitted byJames Polke, on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.174 NOP56 Louise Daugherty edited their review of gene: NOP56: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group. The GREEN review from James Polke on behalf of London North GLH for GMS Neurology specialist test group relates to the STR and not the gene entity (and is indicated in his comments), as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.174 ATXN2_CAG Louise Daugherty changed review comment from: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group.; to: Green rating for STR submitted on behalf of James Polke, on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary ataxia with onset in adulthood v1.174 ATXN10_ATTCT Louise Daugherty changed review comment from: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group.; to: Green rating for STR submitted on behalf of James Polke, on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary ataxia with onset in adulthood v1.174 ATN1_CAG Louise Daugherty changed review comment from: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group. Comment: DRPLA. Triplet repeat. Asked for by Prof Giunti sometimes with ataxia patients with signs of dementia etc.; to: Green rating for STR submitted on behalf of James Polke, on behalf of London North GLH for GMS Neurology specialist test group. Comment: DRPLA. Triplet repeat. Asked for by Prof Giunti sometimes with ataxia patients with signs of dementia etc.
Hereditary ataxia with onset in adulthood v1.174 VAMP1 Louise Daugherty changed review comment from: Review and rating submitted by James Polke (Neurogenetics Laboratory, Institute of Neurology, London) on behalf of London North GLH for GMS Neurology specialist test group


; to: Review and rating submitted by James Polke (Neurogenetics Laboratory, Institute of Neurology, London) on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.174 MAPK8IP3 Eleanor Williams commented on gene: MAPK8IP3
Hereditary ataxia with onset in adulthood v1.171 MSTO1 Louise Daugherty Deleted their comment
Hereditary ataxia with onset in adulthood v1.171 PIK3R5 Louise Daugherty edited their review of gene: PIK3R5: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from London North GLH and Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 PI4KA Louise Daugherty edited their review of gene: PI4KA: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 PCLO Louise Daugherty edited their review of gene: PCLO: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 MME Louise Daugherty edited their review of gene: MME: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH and London North GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 KCNK18 Louise Daugherty edited their review of gene: KCNK18: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH and London North GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 CDK5 Louise Daugherty edited their review of gene: CDK5: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 DCC Louise Daugherty edited their review of gene: DCC: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 DMXL2 Louise Daugherty edited their review of gene: DMXL2: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 FRMD4A Louise Daugherty edited their review of gene: FRMD4A: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 GLI3 Louise Daugherty edited their review of gene: GLI3: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels -Hereditary ataxia v1.148 - Brain channelopathy v1.46. This gene was RED and external expert review from Wessex and West Midlands GLH for GMS Neurology specialist test group for R54 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.171 CCDC88C Louise Daugherty edited their review of gene: CCDC88C: Added comment: This panel was initially created as a merge of genomic entities from the following Rare Disease 100K panels - Early onset dystonia (v1.76, code 192) - Parkinson Disease and Complex Parkinsonism (v1.64, code 39) - Brain channelopathy (v1.48, code 90) - Structural basal ganglia disorders (v1.10, code 180). This gene was RED and external expert review from London North GLH and Wessex and West Midlands GLH for GMS Neurology specialist test group for R56 agrees this gene should remain RED; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.170 TUBB Louise Daugherty Mode of pathogenicity for gene: TUBB was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v1.166 SMPD4 Louise Daugherty edited their review of gene: SMPD4: Added comment: To clarify, this gene was uploaded by the GLH from a gene list submitted for R54. The gene SMPD4 is rated Amber on the following Rare Disease 100K PanelApp panels : Cerebellar hypoplasia, Arthrogryposis, Intellectual disabilit, due to work presented at ESHG 2018 by Pamela Magini: three unrelated families with ID, cerebellar hypoplasia, arthrogryposis. Still unpublished.; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.162 MME Louise Daugherty Mode of inheritance for gene: MME was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.157 DAB1 Louise Daugherty edited their review of gene: DAB1: Added comment: New gene added by Wessex and West Midlands GLH and London North GLH. Gene and Green rating to be discussed by the Neurology Test Group in July 2019 - since this relates to repeat STR entity and not a gene entity. DAB1 STR has not yet been validated by the pipeline.; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.157 BEAN1 Louise Daugherty commented on gene: BEAN1: New gene added by Wessex and West Midlands GLH and London North GLH. Gene and Green rating to be discussed by the Neurology Test Group in July 2019 - since this relates to repeat STR entity and not a gene entity. BEAN1 STR has not yet been validated by the pipeline.
Hereditary ataxia with onset in adulthood v1.157 B3GALNT2 Louise Daugherty Added comment: Comment on list classification: New gene added by Wessex and West Midlands GLH. Gene and Green rating to be discussed by the Neurology Test Group in July 2019.
Hereditary ataxia with onset in adulthood v1.155 ATXN7 Louise Daugherty edited their review of gene: ATXN7: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group. The GREEN review from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH relates to the STR and not the gene entity
(and is indicated in her comments), as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.155 ATXN3 Louise Daugherty edited their review of gene: ATXN3: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group. The GREEN review from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH relates to the STR and not the gene entity (and is indicated in her comments), as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.155 ATXN2 Louise Daugherty edited their review of gene: ATXN2: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group. The GREEN review from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH relates to the STR and not the gene (and is indicated in her comments), as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.155 ATXN10 Louise Daugherty edited their review of gene: ATXN10: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group. The GREEN review from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH relates to the STR and not the gene (and is indicated in her comments), as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.155 ATXN1 Louise Daugherty edited their review of gene: ATXN1: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group. The Green review from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH relates to the STR and not the gene (and is indicated in her comments), as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.155 ATN1 Louise Daugherty edited their review of gene: ATN1: Added comment: This gene was uploaded from the curation template sent out to the GLHs for GMS Neurology specialist test group. The Green review from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH relates to the STR and not the gene (and is indicated in her comments), as there are no SNVs for this gene being associated to the disorder, this gene is rated RED.; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.155 ISCA-37478-Loss Louise Daugherty commented on Region: ISCA-37478-Loss
Hereditary ataxia with onset in adulthood v1.155 ISCA-37478-Gain Louise Daugherty commented on Region: ISCA-37478-Gain: This panel was initially created as a merge of genomic entities form the following Rare Disease 100K two panels : Hereditary ataxia v1.148 and Brain channelopathy v1.46.
This region (rated Green) comes from the Hereditary ataxia v1.148 panel and will need to discussed by the Neurology Test Group in July 2019.
Hereditary ataxia with onset in adulthood v1.155 ISCA-37404-Loss Louise Daugherty commented on Region: ISCA-37404-Loss: This panel was initially created as a merge of genomic entities form the following Rare Disease 100K two panels : Hereditary ataxia v1.148 and Brain channelopathy v1.46.
This region (rated Green) comes from the Hereditary ataxia v1.148 panel and will need to discussed by the Neurology Test Group in July 2019.
Hereditary ataxia with onset in adulthood v1.155 ISCA-37468-Loss Louise Daugherty commented on Region: ISCA-37468-Loss: This panel was initially created as a merge of genomic entities form the following Rare Disease 100K two panels: Hereditary ataxia v1.148 and Brain channelopathy v1.46. This region (rated Green) comes from the Brain channelopathy v1.46 panel, and will need to discussed for inclusion on this panel by the Neurology Test Group in July 2019.
Hereditary ataxia with onset in adulthood v1.155 ATXN8 Louise Daugherty edited their review of gene: ATXN8: Added comment: added tags nucleotide-repeat-expansion and currently-ngs-unreportable; Changed rating: RED
Hereditary ataxia with onset in adulthood v1.155 ATXN8 Louise Daugherty Added comment: Comment on list classification: The gene was added via completed template from expert review for Neurology Test Group but due to the review comments Downgraded to Amber from expert review Green. This potentially is a new STR and if so, needs added as a STR entity, not Gene entity.
Note there is no ENSG ID for this gene for either GRCh38 or GRCh37 so we need to make sure Cellbase has updates
Hereditary ataxia with onset in adulthood v1.139 KCNA2 Louise Daugherty Mode of pathogenicity for gene: KCNA2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v1.124 PACS2 Louise Daugherty Mode of pathogenicity for gene: PACS2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v1.110 RORA Louise Daugherty Mode of pathogenicity for gene: RORA was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v1.107 SAMD9L Louise Daugherty Mode of pathogenicity for gene: SAMD9L was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v1.88 TMEM106B Louise Daugherty Mode of pathogenicity for gene: TMEM106B was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v1.81 TUBA1A Louise Daugherty Mode of pathogenicity for gene: TUBA1A was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v1.78 TUBB2B Louise Daugherty Mode of pathogenicity for gene: TUBB2B was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v1.76 TUBB3 Louise Daugherty Mode of pathogenicity for gene: TUBB3 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v1.68 MTPAP Louise Daugherty Mode of pathogenicity for gene: MTPAP was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v1.50 ATN1 Louise Daugherty Mode of pathogenicity for gene: ATN1 was changed from Other - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v1.40 ZFYVE26 Louise Daugherty Mode of pathogenicity for gene: ZFYVE26 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v1.26 MORC2 Louise Daugherty Mode of pathogenicity for gene: MORC2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v1.22 MFN2 Louise Daugherty Mode of pathogenicity for gene: MFN2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v1.14 TBP_CAG Louise Daugherty commented on STR: TBP_CAG: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group. Comment: SCa17 expansion
Hereditary ataxia with onset in adulthood v1.14 PPP2R2B_CAG Louise Daugherty commented on STR: PPP2R2B_CAG: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group. Comment : SCA 12 expansion
Hereditary ataxia with onset in adulthood v1.14 NOP56_GGCCTG Louise Daugherty commented on STR: NOP56_GGCCTG: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 ATXN7_CAG Louise Daugherty commented on STR: ATXN7_CAG: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 ATXN3_CAG Louise Daugherty commented on STR: ATXN3_CAG: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 ATXN2_CAG Louise Daugherty commented on STR: ATXN2_CAG: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary ataxia with onset in adulthood v1.14 ATXN10_ATTCT Louise Daugherty commented on STR: ATXN10_ATTCT: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary ataxia with onset in adulthood v1.14 ATXN1_CAG Louise Daugherty commented on STR: ATXN1_CAG: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group.
Hereditary ataxia with onset in adulthood v1.14 ATN1_CAG Louise Daugherty commented on STR: ATN1_CAG: Green rating for STR submitted on behalf of James Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group. Comment: DRPLA. Triplet repeat. Asked for by Prof Giunti sometimes with ataxia patients with signs of dementia etc.
Hereditary ataxia with onset in adulthood v1.14 ZFYVE26 Louise Daugherty commented on gene: ZFYVE26: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 XRCC1 Louise Daugherty commented on gene: XRCC1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 VPS13D Louise Daugherty commented on gene: VPS13D: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 VAMP1 Louise Daugherty commented on gene: VAMP1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 TWNK Louise Daugherty commented on gene: TWNK: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 TUBB4A Louise Daugherty commented on gene: TUBB4A: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 TTPA Louise Daugherty commented on gene: TTPA: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 TTC19 Louise Daugherty commented on gene: TTC19: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 TTBK2 Louise Daugherty commented on gene: TTBK2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 TPP1 Louise Daugherty commented on gene: TPP1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 TMEM240 Louise Daugherty commented on gene: TMEM240: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 TINF2 Louise Daugherty commented on gene: TINF2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 TGM6 Louise Daugherty commented on gene: TGM6: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 SYNE1 Louise Daugherty commented on gene: SYNE1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 STUB1 Louise Daugherty commented on gene: STUB1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 SPTBN2 Louise Daugherty commented on gene: SPTBN2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 SPG7 Louise Daugherty commented on gene: SPG7: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 SNX14 Louise Daugherty commented on gene: SNX14: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 SMPD4 Louise Daugherty commented on gene: SMPD4: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 SLC9A1 Louise Daugherty commented on gene: SLC9A1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 SLC25A46 Louise Daugherty commented on gene: SLC25A46: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 SETX Louise Daugherty commented on gene: SETX: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 SAR1B Louise Daugherty commented on gene: SAR1B: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 SAMD9L Louise Daugherty commented on gene: SAMD9L: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 SACS Louise Daugherty commented on gene: SACS: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 RORA Louise Daugherty commented on gene: RORA: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 RNF216 Louise Daugherty commented on gene: RNF216: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 RNF170 Louise Daugherty commented on gene: RNF170: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 PUM1 Louise Daugherty commented on gene: PUM1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 PRRT2 Louise Daugherty commented on gene: PRRT2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 PRNP Louise Daugherty commented on gene: PRNP: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 PRKCG Louise Daugherty commented on gene: PRKCG: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 POLG2 Louise Daugherty commented on gene: POLG2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 POLG Louise Daugherty commented on gene: POLG: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 PNPLA6 Louise Daugherty commented on gene: PNPLA6: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 PLA2G6 Louise Daugherty commented on gene: PLA2G6: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 PIK3R5 Louise Daugherty commented on gene: PIK3R5: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 PDYN Louise Daugherty commented on gene: PDYN: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 PAX2 Louise Daugherty commented on gene: PAX2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 OPA3 Louise Daugherty commented on gene: OPA3: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 NPC2 Louise Daugherty commented on gene: NPC2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 NPC1 Louise Daugherty commented on gene: NPC1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 NHLRC1 Louise Daugherty commented on gene: NHLRC1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 NAGLU Louise Daugherty commented on gene: NAGLU: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 MSTO1 Louise Daugherty commented on gene: MSTO1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 MRE11 Louise Daugherty commented on gene: MRE11: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 MORC2 Louise Daugherty commented on gene: MORC2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 MME Louise Daugherty commented on gene: MME: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 MFN2 Louise Daugherty commented on gene: MFN2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 MARS2 Louise Daugherty commented on gene: MARS2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 KCNK18 Louise Daugherty commented on gene: KCNK18: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 KCND3 Louise Daugherty commented on gene: KCND3: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 KCNC3 Louise Daugherty commented on gene: KCNC3: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 ITPR1 Louise Daugherty commented on gene: ITPR1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 IRF2BPL Louise Daugherty commented on gene: IRF2BPL: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 HTT Louise Daugherty commented on gene: HTT: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 HEXB Louise Daugherty commented on gene: HEXB: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 HEXA Louise Daugherty commented on gene: HEXA: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 GRM1 Louise Daugherty commented on gene: GRM1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 GJC2 Louise Daugherty commented on gene: GJC2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 GFAP Louise Daugherty commented on gene: GFAP: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 GDAP2 Louise Daugherty commented on gene: GDAP2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 GBA2 Louise Daugherty commented on gene: GBA2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 FXN Louise Daugherty commented on gene: FXN: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 FMR1 Louise Daugherty commented on gene: FMR1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 FGF14 Louise Daugherty commented on gene: FGF14: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 EPM2A Louise Daugherty commented on gene: EPM2A: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 ELOVL5 Louise Daugherty commented on gene: ELOVL5: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 ELOVL4 Louise Daugherty commented on gene: ELOVL4: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 EIF2B5 Louise Daugherty commented on gene: EIF2B5: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 EIF2B4 Louise Daugherty commented on gene: EIF2B4: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 EIF2B3 Louise Daugherty commented on gene: EIF2B3: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 EIF2B2 Louise Daugherty commented on gene: EIF2B2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 EIF2B1 Louise Daugherty commented on gene: EIF2B1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 DNMT1 Louise Daugherty commented on gene: DNMT1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 DNAJC5 Louise Daugherty commented on gene: DNAJC5: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 DARS2 Louise Daugherty commented on gene: DARS2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 DAB1 Louise Daugherty commented on gene: DAB1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 CYP27A1 Louise Daugherty commented on gene: CYP27A1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 CSTB Louise Daugherty commented on gene: CSTB: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 CP Louise Daugherty commented on gene: CP: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 COA7 Louise Daugherty commented on gene: COA7: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 CLN6 Louise Daugherty commented on gene: CLN6: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 CLCN2 Louise Daugherty commented on gene: CLCN2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 CCDC88C Louise Daugherty commented on gene: CCDC88C: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 CAPN1 Louise Daugherty commented on gene: CAPN1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 CACNB4 Louise Daugherty commented on gene: CACNB4: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 CACNA1G Louise Daugherty commented on gene: CACNA1G: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 CACNA1A Louise Daugherty commented on gene: CACNA1A: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 BEAN1 Louise Daugherty commented on gene: BEAN1: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 ATP7B Louise Daugherty commented on gene: ATP7B: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 ATP2B3 Louise Daugherty commented on gene: ATP2B3: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 ATP1A3 Louise Daugherty commented on gene: ATP1A3: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 ATP1A2 Louise Daugherty commented on gene: ATP1A2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 ATCAY Louise Daugherty commented on gene: ATCAY: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 ARSA Louise Daugherty commented on gene: ARSA: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 ANO10 Louise Daugherty commented on gene: ANO10: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 AFG3L2 Louise Daugherty commented on gene: AFG3L2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 ADPRHL2 Louise Daugherty commented on gene: ADPRHL2: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 ADCY5 Louise Daugherty commented on gene: ADCY5: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 ABHD12 Louise Daugherty commented on gene: ABHD12: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.14 AARS Louise Daugherty commented on gene: AARS: Review and rating submitted byJames Polke (North Bristol NHS Trust), on behalf of London North GLH for GMS Neurology specialist test group
Hereditary ataxia with onset in adulthood v1.13 MME Louise Daugherty Source London North GMS was added to MME.
Hereditary ataxia with onset in adulthood v1.11 MME James Polke reviewed gene: MME: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary ataxia with onset in adulthood v1.9 MME Louise Daugherty Added phenotypes Spinocerebellar ataxia type 43, 617018 for gene: MME
Hereditary ataxia with onset in adulthood v1.8 TUBB4A Louise Daugherty edited their review of gene: TUBB4A: Added comment: Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group. ; Changed rating: AMBER
Hereditary ataxia with onset in adulthood v1.8 MME Louise Daugherty reviewed gene: MME: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary ataxia with onset in adulthood v1.7 ZNF592 Tracy Lester reviewed gene: ZNF592: Rating: RED; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Galloway-Mowat Syndrome 1, 251300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 ZFYVE26 Tracy Lester reviewed gene: ZFYVE26: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Autosomal recessive spastic paraplegia 15, 270700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 UBR4 Tracy Lester reviewed gene: UBR4: Rating: RED; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Episodic ataxia type 8, 616055; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 TWNK Tracy Lester reviewed gene: TWNK: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 7, 271245, Perrault syndrome 5, 616138, Progressive external ophthalmoplegia with mitochondrial DNA deletions, 609286; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 TUBB4A Tracy Lester reviewed gene: TUBB4A: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Dystonia 4, 128101, Hypomyelinating leukodystrophy 6, 612438; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 TUBB3 Tracy Lester reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Complex cortical dysplasia with other brain abnormalities 1, 614039; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 TUBB2B Tracy Lester reviewed gene: TUBB2B: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Complex cortical dysplasia with other brain abnormalities 7, 610031; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 TUBB2A Tracy Lester reviewed gene: TUBB2A: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Complex cortical dysplasia with other brain malformations 5, 615763; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 TUBB Tracy Lester reviewed gene: TUBB: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Complex cortical dysplasia with other brain malformations 6, 615771; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 TUBA1A Tracy Lester reviewed gene: TUBA1A: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Lissencephaly 3, 611603; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 TMEM240 Tracy Lester reviewed gene: TMEM240: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Spinocerebellar ataxia 21, 607454; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 TMEM106B Tracy Lester reviewed gene: TMEM106B: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Hypomyelinating leukodystrophy 16, 617964; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 SPTBN2 Tracy Lester reviewed gene: SPTBN2: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Spinocerebellar ataxia 5, 600224, Autosomal recessive spinocerebellar ataxia 14, 615386; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 SLC1A3 Tracy Lester reviewed gene: SLC1A3: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Episodic ataxia type 6, 612656; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 SAMD9L Tracy Lester reviewed gene: SAMD9L: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Ataxia-pancytopenia syndrome, 159550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 RORA Tracy Lester reviewed gene: RORA: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Intellectual developmental disorder with or without epilepsy or cerebellar ataxia, 618060; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 RNF170 Tracy Lester reviewed gene: RNF170: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Autosomal dominant sensory ataxia 1, 608984; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 PRNP Tracy Lester reviewed gene: PRNP: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Multiple allelic disorders reported; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 PRKCG Tracy Lester reviewed gene: PRKCG: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Spincocerebellar ataxia 14, 605361; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 POLG Tracy Lester reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Mitochondrial DNA depletion types 4A, 203700 and 4B, 613662, Mitochondrial recessive ataxia syndrome, 607459, autosomal dominant progressive external ophthalmoplegia, 157640 and autosomal recessive progressive external opthalmoplegia, 258450; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 PNKD Tracy Lester reviewed gene: PNKD: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Paroxysmal nonkinesigenic dyskinesia 1, 118800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 PDYN Tracy Lester reviewed gene: PDYN: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Spinocerebellar ataxia 23, 610245; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 PAX2 Tracy Lester reviewed gene: PAX2: Rating: RED; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Papillorenal syndrome, AR; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 PACS2 Tracy Lester reviewed gene: PACS2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Early infantile epileptic encephalopathy 66, 618067; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 OPA1 Tracy Lester reviewed gene: OPA1: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Optic atrophy 1, 165500, Optic atrophy plus syndrome, 125250, Behr syndrome, 210000; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 NAGLU Tracy Lester reviewed gene: NAGLU: Rating: RED; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: CMT axon type 2V, 616491; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 MTPAP Tracy Lester reviewed gene: MTPAP: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Autosomal recessive spastic ataxia 4, 613672; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 MORC2 Tracy Lester reviewed gene: MORC2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Axonal type CMT disease type 2Z, 616688; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 MME Tracy Lester reviewed gene: MME: Rating: RED; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Spinocerebellar ataxia type 43, 617018; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 MFN2 Tracy Lester reviewed gene: MFN2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Dominant optic atrophy plus, not listed in ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 KCNQ3 Tracy Lester reviewed gene: KCNQ3: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Benign neonatal seizures 2, 121201; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 KCNK18 Tracy Lester reviewed gene: KCNK18: Rating: RED; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Susceptibility to migraine with/without arua 13, 613656; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 KCND3 Tracy Lester reviewed gene: KCND3: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Spinocerebellar ataxia 19, 607346; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 KCNC3 Tracy Lester reviewed gene: KCNC3: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Spinocerebellar ataxia 13, 605259; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 KCNA2 Tracy Lester reviewed gene: KCNA2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Early infantile encephalopathy 32, 616366 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 KCNA1 Tracy Lester reviewed gene: KCNA1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Episodic ataxia/myokymia syndrome, 160120; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 ITPR1 Tracy Lester reviewed gene: ITPR1: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Gillespie syndrome, 206700, Spinocerebellar ataxia 15, 606658, Spinocerebellar ataxia 29, 117360; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 HTT Tracy Lester reviewed gene: HTT: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Huntington disease, 143100, 617432; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 GLRA1 Tracy Lester reviewed gene: GLRA1: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Hyperekplexia 1, 149400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v1.7 GFAP Tracy Lester reviewed gene: GFAP: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Alexander disease, 203450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 FMR1 Tracy Lester reviewed gene: FMR1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Fragile X tremor/ataxia syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 ELOVL5 Tracy Lester reviewed gene: ELOVL5: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Spinocerebellar ataxia 38, 615957; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 ELOVL4 Tracy Lester reviewed gene: ELOVL4: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Spinocerebellar ataxia 34, 133190; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 DYNC1H1 Tracy Lester reviewed gene: DYNC1H1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Autosomal dominant MR 13, 614563 most relevant; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 DNMT1 Tracy Lester reviewed gene: DNMT1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Cerebellar ataxia, deafness and narcolepsy, 604121, Hereditary sensory neuropathy type IE, 614116; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 DNAJC5 Tracy Lester reviewed gene: DNAJC5: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Ceroid neuronal lipofuscinosis 4, Parry type, 162350; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 DAB1 Tracy Lester reviewed gene: DAB1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Spinocerebellar ataxia 37, 615945; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 CCDC88C Tracy Lester reviewed gene: CCDC88C: Rating: RED; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Spinocerebellar ataxia 40, 616053; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 CACNB4 Tracy Lester reviewed gene: CACNB4: Rating: RED; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Episodic ataxia type 5, 613855; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 CACNA1G Tracy Lester reviewed gene: CACNA1G: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Spinocerebellar ataxia 42, 616795 and early-onset SCA42 with neurodevelopmental deficits, 618087; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 BEAN1 Tracy Lester reviewed gene: BEAN1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Spinocerebellar ataxia 31, 117210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 ATXN7 Tracy Lester reviewed gene: ATXN7: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Spinocerebellar ataxia 7, 164500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 ATXN3 Tracy Lester reviewed gene: ATXN3: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Machado-Joseph disease, 109150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 ATXN2 Tracy Lester reviewed gene: ATXN2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Spinocerebellar ataxia 2, 183090; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 ATXN10 Tracy Lester reviewed gene: ATXN10: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Spinocerebellar ataxia 10, 603516; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 ATXN1 Tracy Lester reviewed gene: ATXN1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Spinocerebellar ataxia 1, 164400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 ATP2B3 Tracy Lester reviewed gene: ATP2B3: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: X-linked spinocerebellar ataxia, 302500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hereditary ataxia with onset in adulthood v1.7 ATP1A3 Tracy Lester reviewed gene: ATP1A3: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Alternating hemiplegia of childhood 2, 614820, CAPOS syndrome, 601338, Dystonia-12, 128235; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.7 ATP1A2 Tracy Lester reviewed gene: ATP1A2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Alternating hemiplegia of childhood 1, 104290, Familial hemiplegic migraine 2, 602481; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 ATN1 Tracy Lester reviewed gene: ATN1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Dentato-pallidoluysian atrophy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 ADCY5 Tracy Lester reviewed gene: ADCY5: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Dyskinesia with facial myokymia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v1.7 ABCB7 Tracy Lester reviewed gene: ABCB7: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Anemia, sideroblast with ataxia, 300135; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v1.6 TBP_CAG Louise Daugherty commented on STR: TBP_CAG: Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of GMS Neurology specialist test group. Comment: Associated with CAG expansions. Requires STR calling - no evidence for SNVs. Note that median onset described as 23 in OMIM so 'childhood' onset possible. Do you report variants in this gene as part of your current diagnostic practice? No
Hereditary ataxia with onset in adulthood v1.6 PPP2R2B_CAG Louise Daugherty commented on STR: PPP2R2B_CAG: Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of GMS Neurology specialist test group. Comment: Associated with CAG expanions, no evidence for SNVs - requires STR calling. Do you report variants in this gene as part of your current diagnostic practice? No
Hereditary ataxia with onset in adulthood v1.6 NOP56_GGCCTG Louise Daugherty commented on STR: NOP56_GGCCTG: Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of GMS Neurology specialist test group. Comment: Multiple reports in the lit - requires STR reporting, no evidence for SNVs. Do you report variants in this gene as part of your current diagnostic practice? No
Hereditary ataxia with onset in adulthood v1.6 FXN_GAA Louise Daugherty commented on STR: FXN_GAA: Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of GMS Neurology specialist test group. Comment: Needs care with filtering here - SNVs in compound het with expansion can be pathogenic. Needs availability of a mixed STR/SNV model for inheritance OR no filtering of single LoF variants. Do you report variants in this gene as part of your current diagnostic practice? No
Hereditary ataxia with onset in adulthood v1.2 MME Louise Daugherty Source NHS GMS was added to MME.
Hereditary ataxia with onset in adulthood v1.1 MME Louise Daugherty gene: MME was added
gene: MME was added to Hereditary ataxia - adult onset. Sources: Wessex and West Midlands GLH
Mode of inheritance for gene: MME was set to
Hereditary ataxia with onset in adulthood v0.43 TUBB4A Louise Daugherty Added comment: Comment on phenotypes: Implicated autosomal dominant variants in two families with ataxia; hypomyelinating leukodystrophy 6 (612438) - ataxia reported.; Torsion dystonia 4 (128101) - some individuals with ataxia
Hereditary ataxia with onset in adulthood v0.32 TBP_CAG Louise Daugherty STR: TBP_CAG was added
STR: TBP_CAG was added to Hereditary ataxia - adult onset. Sources: Expert list
STR tags were added to STR: TBP_CAG.
Mode of inheritance for STR: TBP_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: TBP_CAG were set to 20301611
Phenotypes for STR: TBP_CAG were set to Spinocerebellar ataxia 17 607136
Review for STR: TBP_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.148;Brain channelopathy v1.46
Sources: Expert list
Hereditary ataxia with onset in adulthood v0.30 PPP2R2B_CAG Louise Daugherty STR: PPP2R2B_CAG was added
STR: PPP2R2B_CAG was added to Hereditary ataxia - adult onset. Sources: Expert list
STR tags were added to STR: PPP2R2B_CAG.
Mode of inheritance for STR: PPP2R2B_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: PPP2R2B_CAG were set to 20301381
Phenotypes for STR: PPP2R2B_CAG were set to Spinocerebellar ataxia 12 604326
Review for STR: PPP2R2B_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia 1.148
Sources: Expert list
Hereditary ataxia with onset in adulthood v0.28 NOP56_GGCCTG Louise Daugherty STR: NOP56_GGCCTG was added
STR: NOP56_GGCCTG was added to Hereditary ataxia - adult onset. Sources: Expert list
STR tags were added to STR: NOP56_GGCCTG.
Mode of inheritance for STR: NOP56_GGCCTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: NOP56_GGCCTG were set to Spinocerebellar ataxia 36 614153
Review for STR: NOP56_GGCCTG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia 1.148
Sources: Expert list
Hereditary ataxia with onset in adulthood v0.26 HTT_CAG Louise Daugherty STR: HTT_CAG was added
STR: HTT_CAG was added to Hereditary ataxia - adult onset. Sources: Expert list
STR tags were added to STR: HTT_CAG.
Mode of inheritance for STR: HTT_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: HTT_CAG were set to Huntington disease 143100
Review for STR: HTT_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia 1.148
Sources: Expert list
Hereditary ataxia with onset in adulthood v0.24 FXN_GAA Louise Daugherty STR: FXN_GAA was added
STR: FXN_GAA was added to Hereditary ataxia - adult onset. Sources: Expert list
STR tags were added to STR: FXN_GAA.
Mode of inheritance for STR: FXN_GAA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for STR: FXN_GAA were set to Friedreich ataxia 229300
Review for STR: FXN_GAA was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia 1.148
Sources: Expert list
Hereditary ataxia with onset in adulthood v0.22 CSTB_CCCCGCCCCGCG Louise Daugherty STR: CSTB_CCCCGCCCCGCG was added
STR: CSTB_CCCCGCCCCGCG was added to Hereditary ataxia - adult onset. Sources: Expert list
STR tags were added to STR: CSTB_CCCCGCCCCGCG.
Mode of inheritance for STR: CSTB_CCCCGCCCCGCG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for STR: CSTB_CCCCGCCCCGCG were set to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800
Review for STR: CSTB_CCCCGCCCCGCG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.148;Brain channelopathy v1.46
Sources: Expert list
Hereditary ataxia with onset in adulthood v0.20 CACNA1A_CAG Louise Daugherty STR: CACNA1A_CAG was added
STR: CACNA1A_CAG was added to Hereditary ataxia - adult onset. Sources: Expert list
STR tags were added to STR: CACNA1A_CAG.
Mode of inheritance for STR: CACNA1A_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: CACNA1A_CAG were set to Spinocerebellar ataxia 6 183086
Review for STR: CACNA1A_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.148;Brain channelopathy v1.46
Sources: Expert list
Hereditary ataxia with onset in adulthood v0.18 ATXN7_CAG Louise Daugherty STR: ATXN7_CAG was added
STR: ATXN7_CAG was added to Hereditary ataxia - adult onset. Sources: Expert list
STR tags were added to STR: ATXN7_CAG.
Mode of inheritance for STR: ATXN7_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: ATXN7_CAG were set to Spinocerebellar ataxia 7 164500
Review for STR: ATXN7_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia 1.148
Sources: Expert list
Hereditary ataxia with onset in adulthood v0.16 ATXN3_CAG Louise Daugherty STR: ATXN3_CAG was added
STR: ATXN3_CAG was added to Hereditary ataxia - adult onset. Sources: Expert list
STR tags were added to STR: ATXN3_CAG.
Mode of inheritance for STR: ATXN3_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: ATXN3_CAG were set to Machado-Joseph disease 109150
Added comment: Source PanelApp panels : Hereditary ataxia 1.148
Sources: Expert list
Hereditary ataxia with onset in adulthood v0.14 ATXN2_CAG Louise Daugherty STR: ATXN2_CAG was added
STR: ATXN2_CAG was added to Hereditary ataxia - adult onset. Sources: Expert list
STR tags were added to STR: ATXN2_CAG.
Mode of inheritance for STR: ATXN2_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: ATXN2_CAG were set to Spinocerebellar ataxia 2 183090
Review for STR: ATXN2_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia 1.148
Sources: Expert list
Hereditary ataxia with onset in adulthood v0.12 ATXN10_ATTCT Louise Daugherty STR: ATXN10_ATTCT was added
STR: ATXN10_ATTCT was added to Hereditary ataxia - adult onset. Sources: Expert list
STR tags were added to STR: ATXN10_ATTCT.
Mode of inheritance for STR: ATXN10_ATTCT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: ATXN10_ATTCT were set to 12164725
Phenotypes for STR: ATXN10_ATTCT were set to Spinocerebellar ataxia 10 603516
Review for STR: ATXN10_ATTCT was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia 1.148
Sources: Expert list
Hereditary ataxia with onset in adulthood v0.9 ATXN1_CAG Louise Daugherty STR: ATXN1_CAG was added
STR: ATXN1_CAG was added to Hereditary ataxia - adult onset. Sources: Expert list
STR tags were added to STR: ATXN1_CAG.
Mode of inheritance for STR: ATXN1_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: ATXN1_CAG were set to Spinocerebellar ataxia 1 164400
Review for STR: ATXN1_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia 1.148
Sources: Expert list
Hereditary ataxia with onset in adulthood v0.6 ATN1_CAG Louise Daugherty STR: ATN1_CAG was added
STR: ATN1_CAG was added to Hereditary ataxia - adult onset. Sources: Expert list
STR tags were added to STR: ATN1_CAG.
Mode of inheritance for STR: ATN1_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: ATN1_CAG were set to entatorubro-pallidoluysian atrophy 125370
Review for STR: ATN1_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia 1.148, Brain channelopathy 1.46
Sources: Expert list
Hereditary ataxia with onset in adulthood v0.2 TUBB4A Eleanor Williams gene: TUBB4A was added
gene: TUBB4A was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Green
Mode of inheritance for gene: TUBB4A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TUBB4A were set to 25497598
Phenotypes for gene: TUBB4A were set to Implicated autosomal dominant variants in two families with ataxia; hypomyelinating leukodystrophy 6 (612438) - ataxia reported.; Torsion dystonia 4 (128101) - some individuals with ataxia
Mode of pathogenicity for gene: TUBB4A was set to Other - please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 TBP Eleanor Williams gene: TBP was added
gene: TBP was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Red
Mode of inheritance for gene: TBP was set to Unknown
Phenotypes for gene: TBP were set to Spinocerebellarataxia17,607136{Parkinsondisease,susceptibilityto},168600
Mode of pathogenicity for gene: TBP was set to Other - please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 PPP2R2B Eleanor Williams gene: PPP2R2B was added
gene: PPP2R2B was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Red
Mode of inheritance for gene: PPP2R2B was set to Unknown
Phenotypes for gene: PPP2R2B were set to Spinocerebellarataxia12,604326
Mode of pathogenicity for gene: PPP2R2B was set to Other - please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 NOP56 Eleanor Williams gene: NOP56 was added
gene: NOP56 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Red
Mode of inheritance for gene: NOP56 was set to Other - please specifiy in evaluation comments
Phenotypes for gene: NOP56 were set to Spinocerebellarataxia36,614153
Mode of pathogenicity for gene: NOP56 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 NAGLU Eleanor Williams gene: NAGLU was added
gene: NAGLU was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Red
Mode of inheritance for gene: NAGLU was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NAGLU were set to 25818867
Phenotypes for gene: NAGLU were set to Sensory neuropathy turning into a mild sensory ataxia (AD); Sanfilippo syndrome B (AR) (OMIM #252920)
Mode of pathogenicity for gene: NAGLU was set to Other - please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 ITPR1 Eleanor Williams gene: ITPR1 was added
gene: ITPR1 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Green
Mode of inheritance for gene: ITPR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ITPR1 were set to Spinocerebellar ataxia 15; Spinocerebellar ataxia 29
Mode of pathogenicity for gene: ITPR1 was set to Other - please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 HTT Eleanor Williams gene: HTT was added
gene: HTT was added to Hereditary ataxia - adult onset. Sources: Brain channelopathy v1.46,Expert Review Red
Mode of inheritance for gene: HTT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: HTT were set to Huntington disease 143100
Mode of pathogenicity for gene: HTT was set to Other - please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 ELOVL5 Eleanor Williams gene: ELOVL5 was added
gene: ELOVL5 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Red
Mode of inheritance for gene: ELOVL5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ELOVL5 were set to Spinocerebellar ataxia 36 615957
Mode of pathogenicity for gene: ELOVL5 was set to Other - please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 DAB1 Eleanor Williams gene: DAB1 was added
gene: DAB1 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Red
Mode of inheritance for gene: DAB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DAB1 were set to 28686858
Phenotypes for gene: DAB1 were set to Spinocerebellar ataxia 37 615945
Mode of pathogenicity for gene: DAB1 was set to Other - please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 CCDC88C Eleanor Williams gene: CCDC88C was added
gene: CCDC88C was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Red
Mode of inheritance for gene: CCDC88C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CCDC88C were set to 25062847
Phenotypes for gene: CCDC88C were set to autosomal dominant spinocerebellar ataxia
Mode of pathogenicity for gene: CCDC88C was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 CACNA1G Eleanor Williams gene: CACNA1G was added
gene: CACNA1G was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Green
Mode of inheritance for gene: CACNA1G was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mode of pathogenicity for gene: CACNA1G was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 ATXN8 Eleanor Williams gene: ATXN8 was added
gene: ATXN8 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Red
Mode of inheritance for gene: ATXN8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATXN8 were set to 10192387
Phenotypes for gene: ATXN8 were set to Spinocerebellar ataxia 8 608768
Mode of pathogenicity for gene: ATXN8 was set to Other - please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 ATXN7 Eleanor Williams gene: ATXN7 was added
gene: ATXN7 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Red
Mode of inheritance for gene: ATXN7 was set to Unknown
Phenotypes for gene: ATXN7 were set to Spinocerebellarataxia 7,164500
Mode of pathogenicity for gene: ATXN7 was set to Other - please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 ATXN3 Eleanor Williams gene: ATXN3 was added
gene: ATXN3 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Red
Mode of inheritance for gene: ATXN3 was set to Unknown
Mode of pathogenicity for gene: ATXN3 was set to Other - please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 ATXN2 Eleanor Williams gene: ATXN2 was added
gene: ATXN2 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Red
Mode of inheritance for gene: ATXN2 was set to Unknown
Phenotypes for gene: ATXN2 were set to {Amyotrophiclateralsclerosis,susceptibilityto,13},183090; Spinocerebellarataxia2, 183090
Mode of pathogenicity for gene: ATXN2 was set to Other - please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 ATXN10 Eleanor Williams gene: ATXN10 was added
gene: ATXN10 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Red
Mode of inheritance for gene: ATXN10 was set to Unknown
Phenotypes for gene: ATXN10 were set to Spinocerebellarataxia10, 603516
Mode of pathogenicity for gene: ATXN10 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 ATXN1 Eleanor Williams gene: ATXN1 was added
gene: ATXN1 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Red
Mode of inheritance for gene: ATXN1 was set to Unknown
Phenotypes for gene: ATXN1 were set to Spinocerebellarataxia1,164400
Mode of pathogenicity for gene: ATXN1 was set to Other - please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 ATN1 Eleanor Williams gene: ATN1 was added
gene: ATN1 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Brain channelopathy v1.46,Expert Review Red
Mode of inheritance for gene: ATN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATN1 were set to Dentatorubro-pallidoluysian atrophy 125370
Mode of pathogenicity for gene: ATN1 was set to Other - please provide details in the comments
Hereditary ataxia with onset in adulthood v0.2 AFG3L2 Eleanor Williams gene: AFG3L2 was added
gene: AFG3L2 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Green
Mode of inheritance for gene: AFG3L2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: AFG3L2 were set to Ataxia, spastic, 5, autosomal recessive; Spinocerebellar Ataxia, Dominant; Spinocerebellar ataxia 28
Mode of pathogenicity for gene: AFG3L2 was set to Other - please provide details in the comments