Activity

Filter

Cancel
Date Panel Item Activity
68 actions
Adult onset neurodegenerative disorder v4.37 SS18L1 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, imprinted status unknown following NHS Genomic Medicine Service approval.
Adult onset neurodegenerative disorder v4.37 SS18L1 Sarah Leigh edited their review of gene: SS18L1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v4.37 SPG7 Sarah Leigh commented on gene: SPG7: The rating of this gene has been updated to Green and the mode of inheritance set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Adult onset neurodegenerative disorder v4.37 SPG21 Sarah Leigh edited their review of gene: SPG21: Added comment: 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.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v4.37 PSAP Sarah Leigh edited their review of gene: PSAP: Added comment: 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.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset neurodegenerative disorder v4.37 NEK1 Sarah Leigh edited their review of gene: NEK1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v4.37 GBE1 Sarah Leigh edited their review of gene: GBE1: Added comment: 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.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v4.37 DNAJB2 Sarah Leigh edited their review of gene: DNAJB2: Added comment: 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.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v4.22 PSAP Sarah Leigh edited their review of gene: PSAP: Added comment: Associated with Parkinson disease 24, autosomal dominant, susceptibility to (OMIM:619491), but not associated with the same condition in Gen2Phen. PMID: 32201884 reports three PSAP variants in three unrelated families with OMIM:619491. Supportive in vitro functional studies were also presented for the reported variants. However, it would appear that there maybe variable expressivity or incomplete penetrance of the Parkinson phenotype, as two variant carrying sibs in Family 2 had extrapyramidal signs, but did not have the full Parkinsons phenotype (PMID: 32201884).; Changed rating: GREEN
Adult onset neurodegenerative disorder v3.49 CLCN2 Arina Puzriakova commented on gene: CLCN2: The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Adult onset neurodegenerative disorder v3.49 XK Arina Puzriakova edited their review of gene: XK: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Adult onset neurodegenerative disorder v2.277 XK Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated Green at the next major review. Neurodegenerative component resembling Huntington disease becomes apparent in older individuals.
Adult onset neurodegenerative disorder v2.275 GBA Sarah Leigh changed review comment from: The new_gene_name tag has been added. The new name for GBA is GBA1.; to: Added new-gene-name tag, new approved HGNC gene symbol for GBA is GBA1.
Adult onset neurodegenerative disorder v2.274 SLC52A3 Arina Puzriakova Added comment: Comment on mode of inheritance: Updated from 'monoallelic' to 'biallelic' as I could not identify evidence supporting relevance of heterozygous variants in disease. This is consistent with the MOI in OMIM/G2P and other PanelApp panels.
Adult onset neurodegenerative disorder v2.268 ISCA-37468-Loss Arina Puzriakova commented on Region: ISCA-37468-Loss: The required percent of overlap for this region has been changed from 80% to 60% following NHS Genomic Medicine Service approval.
Adult onset neurodegenerative disorder v2.268 ISCA-37404-Loss Arina Puzriakova commented on Region: ISCA-37404-Loss: The required percent of overlap for this region has been changed from 80% to 60% and the genomic location has been updated inline with ClinGen following NHS Genomic Medicine Service approval.
Adult onset neurodegenerative disorder v2.263 FIG4 Sarah Leigh commented on gene: FIG4: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Adult onset neurodegenerative disorder v2.263 ERBB4 Sarah Leigh commented on gene: ERBB4: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Adult onset neurodegenerative disorder v2.48 APP Ivone Leong Phenotypes for gene: APP were changed from Alzheimer disease 1, familial OMIM:104300; Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants OMIM:605714 to Alzheimer disease 1, familial, OMIM:104300; Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants, OMIM:605714
Adult onset neurodegenerative disorder v2.38 APP Sarah Leigh Phenotypes for gene: APP were changed from Clinical syndrome Alzheimer disease; Dementia to Alzheimer disease 1, familial OMIM:104300; Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants OMIM:605714
Adult onset neurodegenerative disorder v2.16 DNAJC7 Zornitza Stark gene: DNAJC7 was added
gene: DNAJC7 was added to Neurodegenerative disorders - adult onset. Sources: Literature
Mode of inheritance for gene: DNAJC7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNAJC7 were set to https://doi.org/10.1212/NXG.0000000000000503
Phenotypes for gene: DNAJC7 were set to amyotrophic lateral sclerosis
Review for gene: DNAJC7 was set to AMBER
Added comment: Two cohort studies in ALS patients identified 11 and 1 patient, respectively, with variants in DNAJC7. Seven of these are putative PTVs. No segregation or functional data. A small number of individuals with LOF variants are present in gnomad albeit less than expected. Given these are cohort studies, and an adult-onset condition, potentially of variable penetrance, we have taken a cautious approach and rated Amber for now but would be interested in other expert opinions. No PMID yet.
Sources: Literature
Adult onset neurodegenerative disorder v2.3 APP alisdair mcneill reviewed gene: APP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset neurodegenerative disorder v1.117 TAF1 Louise Daugherty changed review comment from: Comment on list classification: Prior to GLH sign off for this panel, TAF1 was discussed further by the specialist test group. It was raised by WWMGLH that the gene should be downgraded from Green to Red as they were not sure if the pipeline could detect the alu-like insertion variant - and no other variants reported in HGMDPro in association with Dystonia-Parkinsonism. However, further correspondence from LNGLH Huw Morris suggested Amber rating - as per movement disorders on PanelApp. Noting that the genetic aetiology of this disorder is complex and not fully understood; to: Comment on list classification: Prior to GLH sign off for this panel, TAF1 was discussed further by the specialist test group. It was raised by WWMGLH that the gene should be downgraded from Green to Red as they were not sure if the pipeline could detect the alu-like insertion variant - and no other variants reported in HGMDPro in association with Dystonia-Parkinsonism. However, further correspondence from LNGLH Huw Morris suggested an Amber rating - as per movement disorders on PanelApp. Noting that the genetic aetiology of this disorder is complex and not fully understood.
Adult onset neurodegenerative disorder v1.117 TAF1 Louise Daugherty Added comment: Comment on list classification: Prior to GLH sign off for this panel, TAF1 was discussed further by the specialist test group. It was raised by WWMGLH that the gene should be downgraded from Green to Red as they were not sure if the pipeline could detect the alu-like insertion variant - and no other variants reported in HGMDPro in association with Dystonia-Parkinsonism. However, further correspondence from LNGLH Huw Morris suggested Amber rating - as per movement disorders on PanelApp. Noting that the genetic aetiology of this disorder is complex and not fully understood
Adult onset neurodegenerative disorder v1.102 MARS Louise Daugherty commented on gene: MARS: Added new-gene-name tag, new approved HGNC gene symbol for MARS is MARS1
Adult onset neurodegenerative disorder v1.102 AARS Louise Daugherty commented on gene: AARS: Added new-gene-name tag, new approved HGNC gene symbol for AARS is AARS1
Adult onset neurodegenerative disorder v1.102 DARS Louise Daugherty commented on gene: DARS: Added new-gene-name tag, new approved HGNC gene symbol for DARS is DARS1
Adult onset neurodegenerative disorder v1.101 APP Louise Daugherty commented on gene: APP: 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. All the green and amber, except for the genes with triplet repeats, were reviewed.
Adult onset neurodegenerative disorder v1.100 APP Louise Daugherty Source Wessex and West Midlands GLH was added to APP.
Adult onset neurodegenerative disorder v1.99 OPHN1 Tracy Lester reviewed gene: OPHN1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, 300486; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Adult onset neurodegenerative disorder v1.99 APP Tracy Lester reviewed gene: APP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Clinical syndrome Alzheimer disease, Dementia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset neurodegenerative disorder v1.81 PRKRA Louise Daugherty Publications for gene PRKRA were changed from 18420150 - a novel heterozygous variant c.266_267delAT; 25914261; 26990861; 22842711; 24142417 - Compound heterozygous variants were reported in a patient with early onset dystonia c.665C>T (p.P222L) inherited from his mother, and c.637T>C (p.C213R) was a novel mutation; 25142429 In a Polish family, the homozygous p.Pro222Leu mutation segregated with autosomal-recessive, early-onset generalized dystonia and slight parkinsonism; 22842711 describes the clinical features of three original cases with homozygous PRKRA variants - the patients presented with either a pure generalised dystonia or with a dystonia-parkinsonism that was relatively unresponsive to L-dopa; 18243799; 25142429; http://www.ncbi.nlm.nih.gov/books/NBK1155/; 18420150; p.H89fsX20 was reported in a proband with early childhood-onset leg dystonia (though testing in the parents was not mentioned).; 24142417; 25737287 Compound het variants (c.G230C (p.Cys77Ser), and in exon 7, c.G638T (p.Cys213Phe)) identified in the two affected siblings reported with dystonia without parkinsonism, unaffected family members were heterozygous; PMID: 26990861 - c.665C>T homozygous variant was identified in 3 affected siblings with Early-Onset Generalized Dystonia-Parkinsonism (and was heterozygous in the unaffected patients and an unaffected sibling). It was confirmed by Sanger sequencing and had a frequency of 0.01% in the Exome Aggregation Consortium database, predicted to be deleterious by 2 of 6 in silico tools. They showed it was within a founder haplotype shared by all previoulsy reported cases. The Authors state Screening of PRKRA is warranted in all patients with early-onset generalized dystonia, or dystonia parkinsonism compatible with autosomal recessive inheritance; 18243799 - two unrelated families with members with an apparent autosomal recessive, novel, young-onset, generalised form of dystonia parkinsonism. A region of homozygosity was found in all affected individuals, and narrowed down to the homozygous variant c.665C>T (P222L); 25737287 to 24142417; 25737287 26990861; 18420150.; 25914261; 25737287; 18243799; 26990861; http://www.ncbi.nlm.nih.gov/books/NBK1155/; 18420150; 22842711; 25142429
Adult onset neurodegenerative disorder v1.81 APP Louise Daugherty Publications for gene APP were changed from 22503161; 23028126 to 2111584; 23028126; 22503161
Adult onset neurodegenerative disorder v1.80 PRKRA Louise Daugherty changed review comment from: 18420150 - a novel heterozygous variant c.266_267delAT;25914261;26990861;22842711;24142417 - Compound heterozygous variants were reported in a patient with early onset dystonia c.665C>T (p.P222L) inherited from his mother, and c.637T>C (p.C213R) was a novel mutation;25142429 In a Polish family, the homozygous p.Pro222Leu mutation segregated with autosomal-recessive, early-onset generalized dystonia and slight parkinsonism;22842711 describes the clinical features of three original cases with homozygous PRKRA variants - the patients presented with either a pure generalised dystonia or with a dystonia-parkinsonism that was relatively unresponsive to L-dopa;18243799;25142429;http://www.ncbi.nlm.nih.gov/books/NBK1155/;18420150;p.H89fsX20 was reported in a proband with early childhood-onset leg dystonia (though testing in the parents was not mentioned).;24142417;25737287 Compound het variants (c.G230C (p.Cys77Ser), and in exon 7, c.G638T (p.Cys213Phe)) identified in the two affected siblings reported with dystonia without parkinsonism, unaffected family members were heterozygous;PMID: 26990861 - c.665C>T homozygous variant was identified in 3 affected siblings with Early-Onset Generalized Dystonia-Parkinsonism (and was heterozygous in the unaffected patients and an unaffected sibling). It was confirmed by Sanger sequencing and had a frequency of 0.01% in the Exome Aggregation Consortium database, predicted to be deleterious by 2 of 6 in silico tools. They showed it was within a founder haplotype shared by all previoulsy reported cases. The Authors state Screening of PRKRA is warranted in all patients with early-onset generalized dystonia, or dystonia parkinsonism compatible with autosomal recessive inheritance;18243799 - two unrelated families with members with an apparent autosomal recessive, novel, young-onset, generalised form of dystonia parkinsonism. A region of homozygosity was found in all affected individuals, and narrowed down to the homozygous variant c.665C>T (P222L);25737287; to: Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.
Created: 23 Jul 2019, 3:51 p.m. | Last Modified: 23 Jul 2019, 3:51 p.m.

Panel Version: 1.74

Edit your comment Delete comment
Review and rating submitted byJames Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.
Created: 23 Apr 2019, 5:35 p.m.
Adult onset neurodegenerative disorder v1.80 PRKRA Louise Daugherty commented on gene: PRKRA: 18420150 - a novel heterozygous variant c.266_267delAT;25914261;26990861;22842711;24142417 - Compound heterozygous variants were reported in a patient with early onset dystonia c.665C>T (p.P222L) inherited from his mother, and c.637T>C (p.C213R) was a novel mutation;25142429 In a Polish family, the homozygous p.Pro222Leu mutation segregated with autosomal-recessive, early-onset generalized dystonia and slight parkinsonism;22842711 describes the clinical features of three original cases with homozygous PRKRA variants - the patients presented with either a pure generalised dystonia or with a dystonia-parkinsonism that was relatively unresponsive to L-dopa;18243799;25142429;http://www.ncbi.nlm.nih.gov/books/NBK1155/;18420150;p.H89fsX20 was reported in a proband with early childhood-onset leg dystonia (though testing in the parents was not mentioned).;24142417;25737287 Compound het variants (c.G230C (p.Cys77Ser), and in exon 7, c.G638T (p.Cys213Phe)) identified in the two affected siblings reported with dystonia without parkinsonism, unaffected family members were heterozygous;PMID: 26990861 - c.665C>T homozygous variant was identified in 3 affected siblings with Early-Onset Generalized Dystonia-Parkinsonism (and was heterozygous in the unaffected patients and an unaffected sibling). It was confirmed by Sanger sequencing and had a frequency of 0.01% in the Exome Aggregation Consortium database, predicted to be deleterious by 2 of 6 in silico tools. They showed it was within a founder haplotype shared by all previoulsy reported cases. The Authors state Screening of PRKRA is warranted in all patients with early-onset generalized dystonia, or dystonia parkinsonism compatible with autosomal recessive inheritance;18243799 - two unrelated families with members with an apparent autosomal recessive, novel, young-onset, generalised form of dystonia parkinsonism. A region of homozygosity was found in all affected individuals, and narrowed down to the homozygous variant c.665C>T (P222L);25737287
Adult onset neurodegenerative disorder v1.78 CHMP2B Louise Daugherty commented on gene: CHMP2B: Comment: - PMID: 20352044 conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype.
Adult onset neurodegenerative disorder v1.78 CHMP2B Louise Daugherty changed review comment from: Review and rating submitted byJames Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group. Comment: - We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype.; to: Review and rating submitted byJames Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.
Adult onset neurodegenerative disorder v1.78 CHMP2B Louise Daugherty changed review comment from: Review and rating submitted byJames Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.; to: Review and rating submitted byJames Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group. Comment: - We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype.
Adult onset neurodegenerative disorder v1.78 CHMP2B Louise Daugherty Publications for gene: CHMP2B were set to PMID: 20352044 - We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype.
Adult onset neurodegenerative disorder v1.74 APP Louise Daugherty commented on gene: APP: Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.
Adult onset neurodegenerative disorder v1.72 OPHN1 Nick Beauchamp reviewed gene: OPHN1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, 300486; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Adult onset neurodegenerative disorder v1.72 APP Nick Beauchamp reviewed gene: APP: Rating: GREEN; Mode of pathogenicity: ; Publications: 2111584; Phenotypes: Clinical syndrome Alzheimer disease, Dementia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Adult onset neurodegenerative disorder v1.67 APP Louise Daugherty Source Yorkshire and North East GLH was added to APP.
Adult onset neurodegenerative disorder v1.45 KIAA1161 Louise Daugherty commented on gene: KIAA1161: added new-gene-name tag, new approved HGNC gene symbol for KIAA1161 is MYORG
Adult onset neurodegenerative disorder v1.11 APP Louise Daugherty reviewed gene: APP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset neurodegenerative disorder v1.10 APP James Polke reviewed gene: APP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Adult onset neurodegenerative disorder v1.9 APP Louise Daugherty Source NHS GMS was added to APP.
Adult onset neurodegenerative disorder v1.8 APP Louise Daugherty Source London North GLH was added to APP.
Adult onset neurodegenerative disorder v0.125 OPHN1 Louise Daugherty Phenotypes for gene: OPHN1 were changed from to Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, 300486
Adult onset neurodegenerative disorder v0.78 AR_CAG Louise Daugherty STR: AR_CAG was added
STR: AR_CAG was added to Neurodegenerative disorders - adult onset. Sources: Expert list
STR tags were added to STR: AR_CAG.
Mode of inheritance for STR: AR_CAG 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: AR_CAG were set to Spinal and bulbar muscular atrophy or Kennedy diseases 313200
Added comment: Source PanelApp panels : Amyotrophic lateral sclerosis/motor neuron disease v1.26
Sources: Expert list
Adult onset neurodegenerative disorder v0.76 ATN1_CAG Louise Daugherty STR: ATN1_CAG was added
STR: ATN1_CAG was added to Neurodegenerative disorders - 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
Publications for STR: ATN1_CAG were set to 20301664; 8136840; 20301664; 8136840; 8136826; 7614090
Phenotypes for STR: ATN1_CAG were set to Dentatorubro-pallidoluysian atrophy 125370
Review for STR: ATN1_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.150, Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.46, Brain channelopathy v1.48, Parkinson Disease and Complex Parkinsonism v1.64.
Sources: Expert list
Adult onset neurodegenerative disorder v0.74 ATXN10_ATTCT Louise Daugherty STR: ATXN10_ATTCT was added
STR: ATXN10_ATTCT was added to Neurodegenerative disorders - 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
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 spastic paraplegia v1.143, Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.46, Hereditary ataxia v1.150
Sources: Expert list
Adult onset neurodegenerative disorder v0.72 ATXN1_CAG Louise Daugherty STR: ATXN1_CAG was added
STR: ATXN1_CAG was added to Neurodegenerative disorders - 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 v1.150, Hereditary spastic paraplegia v1.143, Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.46, Parkinson Disease and Complex Parkinsonism v1.64.
Sources: Expert list
Adult onset neurodegenerative disorder v0.70 ATXN2_CAG Louise Daugherty STR: ATXN2_CAG was added
STR: ATXN2_CAG was added to Neurodegenerative disorders - 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 v1.150, Hereditary spastic paraplegia v1.143, Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.46, Early onset dystonia v1.76, Parkinson Disease and Complex Parkinsonism v1.64.
Sources: Expert list
Adult onset neurodegenerative disorder v0.65 ATXN3_CAG Louise Daugherty STR: ATXN3_CAG was added
STR: ATXN3_CAG was added to Neurodegenerative disorders - 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
Review for STR: ATXN3_CAG was set to GREEN
Added comment: Source PanelApp panels : Early onset dystonia v1.76, Parkinson Disease and Complex Parkinsonism v1.64, Hereditary ataxia v1.150, Hereditary spastic paraplegia v1.143.
Sources: Expert list
Adult onset neurodegenerative disorder v0.63 CSTB_CCCCGCCCCGCG Louise Daugherty STR: CSTB_CCCCGCCCCGCG was added
STR: CSTB_CCCCGCCCCGCG was added to Neurodegenerative disorders - 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 : Brain channelopathy v1.48, Hereditary ataxia v1.150.
Sources: Expert list
Adult onset neurodegenerative disorder v0.61 FXN_GAA Louise Daugherty STR: FXN_GAA was added
STR: FXN_GAA was added to Neurodegenerative disorders - 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 spastic paraplegia v1.143, Hereditary ataxia v1.150
Sources: Expert list
Adult onset neurodegenerative disorder v0.59 HTT_CAG Louise Daugherty STR: HTT_CAG was added
STR: HTT_CAG was added to Neurodegenerative disorders - 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 spastic paraplegia v1.143, Parkinson Disease and Complex Parkinsonism v1.64, Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.46, Hereditary ataxia v1.150
Sources: Expert list
Adult onset neurodegenerative disorder v0.57 ATXN7_CAG Louise Daugherty STR: ATXN7_CAG was added
STR: ATXN7_CAG was added to Neurodegenerative disorders - 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 spastic paraplegia v1.141, Hereditary ataxia v1.148.
Sources: Expert list
Adult onset neurodegenerative disorder v0.55 C9orf72_GGGGCC Louise Daugherty STR: C9orf72_GGGGCC was added
STR: C9orf72_GGGGCC was added to Neurodegenerative disorders - adult onset. Sources: Expert list
STR tags were added to STR: C9orf72_GGGGCC.
Mode of inheritance for STR: C9orf72_GGGGCC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: C9orf72_GGGGCC were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550
Review for STR: C9orf72_GGGGCC was set to GREEN
Added comment: Source PanelApp panels : Parkinson Disease and Complex Parkinsonism v1.64, Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.45, Amyotrophic lateral sclerosis/motor neuron disease v1.26
Sources: Expert list
Adult onset neurodegenerative disorder v0.53 CACNA1A_CAG Louise Daugherty STR: CACNA1A_CAG was added
STR: CACNA1A_CAG was added to Neurodegenerative disorders - 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, Hereditary spastic paraplegia v1.141.
Sources: Expert list
Adult onset neurodegenerative disorder v0.51 JPH3_CTG Louise Daugherty STR: JPH3_CTG was added
STR: JPH3_CTG was added to Neurodegenerative disorders - adult onset. Sources: Expert list
STR tags were added to STR: JPH3_CTG.
Mode of inheritance for STR: JPH3_CTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: JPH3_CTG were set to Huntington disease-like 2 606438
Review for STR: JPH3_CTG was set to GREEN
Added comment: Source PanelApp panels : Parkinson Disease and Complex Parkinsonism v1.64, Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.45, Early onset dystonia v1.76.
Sources: Expert list
Adult onset neurodegenerative disorder v0.49 NOP56_GGCCTG Louise Daugherty STR: NOP56_GGCCTG was added
STR: NOP56_GGCCTG was added to Neurodegenerative disorders - 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 v1.148, Amyotrophic lateral sclerosis/motor neuron disease v1.26, Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.45.
Sources: Expert list
Adult onset neurodegenerative disorder v0.38 PPP2R2B_CAG Louise Daugherty STR: PPP2R2B_CAG was added
STR: PPP2R2B_CAG was added to Neurodegenerative disorders - 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 : Parkinson Disease and Complex Parkinsonism v1.64, Hereditary spastic paraplegia v1.141, Hereditary ataxia v1.148
Sources: Expert list
Adult onset neurodegenerative disorder v0.36 TBP_CAG Louise Daugherty STR: TBP_CAG was added
STR: TBP_CAG was added to Neurodegenerative disorders - 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, Parkinson Disease and Complex Parkinsonism v1.64, Hereditary spastic paraplegia v1.141, Brain channelopathy v1.46, Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.45
Sources: Expert list
Adult onset neurodegenerative disorder v0.2 PRKRA Rebecca Foulger gene: PRKRA was added
gene: PRKRA was added to Neurodegenerative disorders - adult onset. Sources: Expert Review Green
Mode of inheritance for gene: PRKRA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKRA were set to 18420150 - a novel heterozygous variant c.266_267delAT; 25914261; 26990861; 22842711; 24142417 - Compound heterozygous variants were reported in a patient with early onset dystonia c.665C>T (p.P222L) inherited from his mother, and c.637T>C (p.C213R) was a novel mutation; 25142429 In a Polish family, the homozygous p.Pro222Leu mutation segregated with autosomal-recessive, early-onset generalized dystonia and slight parkinsonism; 22842711 describes the clinical features of three original cases with homozygous PRKRA variants - the patients presented with either a pure generalised dystonia or with a dystonia-parkinsonism that was relatively unresponsive to L-dopa; 18243799; 25142429; http://www.ncbi.nlm.nih.gov/books/NBK1155/; 18420150; p.H89fsX20 was reported in a proband with early childhood-onset leg dystonia (though testing in the parents was not mentioned).; 24142417; 25737287 Compound het variants (c.G230C (p.Cys77Ser), and in exon 7, c.G638T (p.Cys213Phe)) identified in the two affected siblings reported with dystonia without parkinsonism, unaffected family members were heterozygous; PMID: 26990861 - c.665C>T homozygous variant was identified in 3 affected siblings with Early-Onset Generalized Dystonia-Parkinsonism (and was heterozygous in the unaffected patients and an unaffected sibling). It was confirmed by Sanger sequencing and had a frequency of 0.01% in the Exome Aggregation Consortium database, predicted to be deleterious by 2 of 6 in silico tools. They showed it was within a founder haplotype shared by all previoulsy reported cases. The Authors state Screening of PRKRA is warranted in all patients with early-onset generalized dystonia, or dystonia parkinsonism compatible with autosomal recessive inheritance; 18243799 - two unrelated families with members with an apparent autosomal recessive, novel, young-onset, generalised form of dystonia parkinsonism. A region of homozygosity was found in all affected individuals, and narrowed down to the homozygous variant c.665C>T (P222L); 25737287
Phenotypes for gene: PRKRA were set to Dystonia 16; early-onset generalized dystonia-parkinsonism (DYT16), non-responsive to levo-dopa; Early-Onset Generalized Dystonia-Parkinsonism; Early Onset Complex Disease
Adult onset neurodegenerative disorder v0.2 CHMP2B Rebecca Foulger gene: CHMP2B was added
gene: CHMP2B was added to Neurodegenerative disorders - adult onset. Sources: Expert Review Green
Mode of inheritance for gene: CHMP2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CHMP2B were set to PMID: 20352044 - We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype.
Phenotypes for gene: CHMP2B were set to Dementia, familial, nonspecific, 600795Amyotrophic lateral sclerosis 17, 614696; Frontotemporal Dementia
Adult onset neurodegenerative disorder v0.2 APP Rebecca Foulger gene: APP was added
gene: APP was added to Neurodegenerative disorders - adult onset. Sources: Expert Review Green
Mode of inheritance for gene: APP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APP were set to 22503161; 23028126
Phenotypes for gene: APP were set to Clinical syndrome Alzheimer disease; Dementia