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Early onset dystonia v1.147 KMT2B Arina Puzriakova Phenotypes for gene: KMT2B were changed from early-onset dystonia to Dystonia 28, childhood-onset, OMIM:617284; early-onset dystonia
Early onset dystonia v1.146 ARX Sarah Leigh Classified gene: ARX as Green List (high evidence)
Early onset dystonia v1.146 ARX Sarah Leigh Gene: arx has been classified as Green List (High Evidence).
Early onset dystonia v1.145 ARX Sarah Leigh Phenotypes for gene: ARX were changed from Dystonia to Developmental and epileptic encephalopathy 1, OMIM:308350; X-linked spasticity-intellectual disability-epilepsy syndromeMONDO:0017856; Partington syndrome, OMIM:309510; Partington syndrome, MONDO:0010654
Early onset dystonia v1.144 ARX Sarah Leigh Publications for gene: ARX were set to
Early onset dystonia v1.143 FOXG1 Arina Puzriakova Phenotypes for gene: FOXG1 were changed from Dystonia to Rett Syndrome, congenital variant OMIM:613454
Early onset dystonia v1.142 FOXG1 Arina Puzriakova Publications for gene: FOXG1 were set to
Early onset dystonia v1.141 FOXG1 Arina Puzriakova Classified gene: FOXG1 as Green List (high evidence)
Early onset dystonia v1.141 FOXG1 Arina Puzriakova Gene: foxg1 has been classified as Green List (High Evidence).
Early onset dystonia v1.140 FOXG1 Arina Puzriakova Classified gene: FOXG1 as Red List (low evidence)
Early onset dystonia v1.140 FOXG1 Arina Puzriakova Added comment: Comment on list classification: Upgrading the rating from red to green as there is enough evidence to support the gene-disease association. Also green on the childhood dystonia GMS panel (R57).
Early onset dystonia v1.140 FOXG1 Arina Puzriakova Gene: foxg1 has been classified as Red List (Low Evidence).
Early onset dystonia v1.139 FOXG1 Arina Puzriakova Mode of inheritance for gene: FOXG1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset dystonia v1.138 AFG3L2 Arina Puzriakova Classified gene: AFG3L2 as Green List (high evidence)
Early onset dystonia v1.138 AFG3L2 Arina Puzriakova Added comment: Comment on list classification: Associated with AR and AD ataxia. Dystonia can be a feature but is not typically prominent. Mean age of onset is adulthood, but has been reported in juveniles. More appropriate on ataxia panels.
However, is rated as green on equivalent GMS panels and therefore upgrading the rating from red to green on this 100K panel.
Early onset dystonia v1.138 AFG3L2 Arina Puzriakova Gene: afg3l2 has been classified as Green List (High Evidence).
Early onset dystonia v1.137 AFG3L2 Arina Puzriakova Phenotypes for gene: AFG3L2 were changed from Dystonia to Spinocerebellar ataxia 28, OMIM:610246; Spastic ataxia 5, autosomal recessive, OMIM:614487
Early onset dystonia v1.136 AFG3L2 Arina Puzriakova Mode of inheritance for gene: AFG3L2 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset dystonia v1.135 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND6.
Early onset dystonia v1.135 SPATA5L1 Achchuthan Shanmugasundram commented on gene: SPATA5L1
Early onset dystonia v1.135 SPATA5L1 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: SPATA5L1.
Early onset dystonia v1.135 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing tag was added to gene: MT-ND6.
Early onset dystonia v1.135 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Neurodegeneration with brain iron accumulation 6; COASY protein-associated neurodegeneration to Neurodegeneration with brain iron accumulation 6, OMIM:615643; neurodegeneration with brain iron accumulation 6, MONDO:0014290
Early onset dystonia v1.134 COASY Sarah Leigh Publications for gene: COASY were set to 27021474
Early onset dystonia v1.133 VPS11 Sarah Leigh Classified gene: VPS11 as Amber List (moderate evidence)
Early onset dystonia v1.133 VPS11 Sarah Leigh Gene: vps11 has been classified as Amber List (Moderate Evidence).
Early onset dystonia v1.132 VPS11 Sarah Leigh reviewed gene: VPS11: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset dystonia v1.132 VPS11 Sarah Leigh Phenotypes for gene: VPS11 were changed from Neurodevelopmental disorder; Hypomyelination; Microcephaly; Infantile-onset dystonia; Adult-onset dystonia; Spasticity to ?Dystonia 32, OMIM:619637; dystonia 32, MONDO:0030486
Early onset dystonia v1.131 VPS11 Sarah Leigh Publications for gene: VPS11 were set to PMID: 33452836; 27120463; 27473128; 33871597
Early onset dystonia v1.130 VPS11 Edoardo Monfrini gene: VPS11 was added
gene: VPS11 was added to Early onset dystonia. Sources: Literature
Mode of inheritance for gene: VPS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS11 were set to PMID: 33452836; 27120463; 27473128; 33871597
Phenotypes for gene: VPS11 were set to Neurodevelopmental disorder; Hypomyelination; Microcephaly; Infantile-onset dystonia; Adult-onset dystonia; Spasticity
Penetrance for gene: VPS11 were set to Complete
Review for gene: VPS11 was set to GREEN
gene: VPS11 was marked as current diagnostic
Added comment: Early-onset patients present hypomyelination, developmental delay, spasticity and dystonia.

A single adult-onset generalized dystonic patient without additional neurologic signs has been reported. This genetic association needs additional cases to be definitively confirmed.
Sources: Literature
Early onset dystonia v1.130 ADAR Arina Puzriakova Phenotypes for gene: ADAR were changed from Aicardi-Goutieres syndrome 6, 615010; dystonia to Aicardi-Goutieres syndrome 6, OMIM:615010; Dyschromatosis symmetrica hereditaria, OMIM:127400
Early onset dystonia v1.129 ADAR Arina Puzriakova Added comment: Comment on mode of inheritance: Updated from biallelic only to both mono- and biallelic.

Dystonia is an established feature of AGS6 (MIM# 615010) associated with AR variants in this gene. Overall the AD condition (dyschromatosis symmetrica hereditaria, MIM# 127400) often presents with changes in skin pigmentation as the only sign of disease. However, there have also been reports of neurologic deficits including ID, developmental regression, brain calcification, seizures and dystonia in some affected individuals, particularly with the Gly1007Arg variant (PMID: 16225627; 16817193; 19017046). Although the penetrance of extracutaneous features is reduced, there is value in testing heterozygous ADAR variants on these panels to ensure syndromic cases are not missed if not tested in the context of the skin phenotype.
Early onset dystonia v1.129 ADAR Arina Puzriakova Mode of inheritance for gene: ADAR was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset dystonia v1.128 XK Sarah Leigh Classified gene: XK as Red List (low evidence)
Early onset dystonia v1.128 XK Sarah Leigh Gene: xk has been classified as Red List (Low Evidence).
Early onset dystonia v1.127 XK Sarah Leigh edited their review of gene: XK: Changed rating: RED
Early onset dystonia v1.127 XK Sarah Leigh reviewed gene: XK: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset dystonia v1.127 XK Sarah Leigh Publications for gene: XK were set to 11761473; 8004674; 11032622; 11261514
Early onset dystonia v1.126 XK Sarah Leigh Publications for gene: XK were set to 11761473; 11761473
Early onset dystonia v1.125 HPRT1 Sarah Leigh Phenotypes for gene: HPRT1 were changed from Lesch-Nyhan syndrome, OMIM:300322; Dystonia to Lesch-Nyhan syndrome, OMIM:300322
Early onset dystonia v1.124 HPRT1 Sarah Leigh Classified gene: HPRT1 as Green List (high evidence)
Early onset dystonia v1.124 HPRT1 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numous variants have been reported in Lesch-Nyhan syndrome (OMIM:300322) cases.
Early onset dystonia v1.124 HPRT1 Sarah Leigh Gene: hprt1 has been classified as Green List (High Evidence).
Early onset dystonia v1.123 HPRT1 Sarah Leigh Publications for gene: HPRT1 were set to
Early onset dystonia v1.122 FASTKD2 Arina Puzriakova Mode of inheritance for gene: FASTKD2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset dystonia v1.121 FASTKD2 Arina Puzriakova Phenotypes for gene: FASTKD2 were changed from Dystonia to Combined oxidative phosphorylation deficiency 44, OMIM:618855; Dystonia
Early onset dystonia v1.120 HPRT1 Eldar Dedic changed review comment from: Jinnah, et al. (2006) studied 44 Lesch–Nyhan disease patients (age range between 2 and 38 years; only one of them was female; all experienced severe dystonia). Multiple rare HPRT1 variants (including at least 2 splice site variants (IVS6-1G>A (also known as c.486-1G>A), and IVS4+1G>A (also known as c.384+1G>A)), as well as exon 1 deletion, and exon 9 deletion) in patients (the majority of which were under 31 years of age when they were first seen by a clinician) with hypoxanthine-guanine phosphoribosyltransferase activity below 1% have been reported. As of August 2022, the c.384+1G>A and c.384+1G>A variants were absent from gnomAD version 2.1.1, and no high-frequency structural variants have been reported in gnomAD SVs v2.1 either.; to: Jinnah, et al. (2006) studied 44 Lesch–Nyhan disease patients (age range between 2 and 38 years; only one of them was female; all experienced severe dystonia). Multiple rare HPRT1 variants (including at least 2 splice site variants (IVS6-1G>A (also known as c.486-1G>A), and IVS4+1G>A (also known as c.384+1G>A)), as well as exon 1 deletion, and exon 9 deletion) in patients (the majority of which were under 31 years of age when they were first seen by a clinician) with hypoxanthine-guanine phosphoribosyltransferase activity below 1% have been reported. As of August 2022, the c.486-1G>A and c.384+1G>A variants were absent from gnomAD version 2.1.1, and no high-frequency structural variants have been reported in gnomAD SVs v2.1 either.
Early onset dystonia v1.120 HPRT1 Eldar Dedic changed review comment from: Jinnah, et al. (2006) studied 44 Lesch–Nyhan disease patients (age range between 2 and 38 years; only one of them was female; all experienced severe dystonia). Multiple rare HPRT1 variants (including at least 2 splice site variants (IVS6-1G>A (also known as c.486-1G>A), and IVS4+1G>A (also known as c.384+1G>A)), as well as exon 1 deletion, and exon 9 deletion) in patients (the majority of which were under 31 years of age when they were first seen by a clinician) with hypoxanthine-guanine phosphoribosyltransferase activity below 1% have been reported. As of August 2022, all variants were absent from gnomAD version 2.1.1, and no high-frequency structural variants have been reported in gnomAD SVs v2.1 either.; to: Jinnah, et al. (2006) studied 44 Lesch–Nyhan disease patients (age range between 2 and 38 years; only one of them was female; all experienced severe dystonia). Multiple rare HPRT1 variants (including at least 2 splice site variants (IVS6-1G>A (also known as c.486-1G>A), and IVS4+1G>A (also known as c.384+1G>A)), as well as exon 1 deletion, and exon 9 deletion) in patients (the majority of which were under 31 years of age when they were first seen by a clinician) with hypoxanthine-guanine phosphoribosyltransferase activity below 1% have been reported. As of August 2022, the c.384+1G>A and c.384+1G>A variants were absent from gnomAD version 2.1.1, and no high-frequency structural variants have been reported in gnomAD SVs v2.1 either.
Early onset dystonia v1.120 HPRT1 Eldar Dedic reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16549399; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset dystonia v1.120 NDUFA12 Arina Puzriakova Classified gene: NDUFA12 as Green List (high evidence)
Early onset dystonia v1.120 NDUFA12 Arina Puzriakova Added comment: Comment on list classification: Gene was recently upgraded to Green on GMS panels and therefore also updating the rating here to ensure all panels display correct knowledge.
Early onset dystonia v1.120 NDUFA12 Arina Puzriakova Gene: ndufa12 has been classified as Green List (High Evidence).
Early onset dystonia v1.119 NDUFA12 Arina Puzriakova reviewed gene: NDUFA12: Rating: GREEN; Mode of pathogenicity: None; Publications: 21617257, 33715266, 35141356; Phenotypes: Mitochondrial complex I deficiency, nuclear type 23, OMIM:618244; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset dystonia v1.119 NDUFA12 Arina Puzriakova Phenotypes for gene: NDUFA12 were changed from Leigh syndrome due to mitochondrial complex 1 deficiency 256000 to Mitochondrial complex I deficiency, nuclear type 23, OMIM:618244
Early onset dystonia v1.118 NDUFA12 Arina Puzriakova Publications for gene: NDUFA12 were set to 21617257
Early onset dystonia v1.117 C19orf12 Sarah Leigh Added comment: Comment on mode of inheritance: Monfrini et al (PMID: 29295770) and Gregory et al (PMID: 31087512) have reported heterozygous pathogenic C19ORF12 variants in patients with neurodegeneration with brain iron accumulation 4 (OMIM: 614298). Therefore, the mode of inheritance for this gene should be BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Early onset dystonia v1.117 C19orf12 Sarah Leigh Mode of inheritance for gene: C19orf12 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset dystonia v1.116 C19orf12 Sarah Leigh Phenotypes for gene: C19orf12 were changed from Dystonia; mitochondrial membrane protein-associated neurodegeneration; neurodegeneration with brain iron accumulation-4 to ?Spastic paraplegia 43, autosomal recessive, OMIM:615043; Neurodegeneration with brain iron accumulation 4, OMIM: 614298
Early onset dystonia v1.115 C19orf12 Sarah Leigh Mode of inheritance for gene: C19orf12 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset dystonia v1.114 C19orf12 Sarah Leigh Publications for gene: C19orf12 were set to
Early onset dystonia v1.113 TOR1A Arina Puzriakova Phenotypes for gene: TOR1A were changed from Dystonia-1, torsion, OMIM:128100; Dystonic disorder, MONDO:0003441 to Dystonia-1, torsion, OMIM:128100; Arthrogryposis multiplex congenita 5, OMIM:618947
Early onset dystonia v1.112 TOR1A Arina Puzriakova Added comment: Comment on mode of inheritance: Dystonia association with monoallelic variants is well-established with multiple cases reported worldwide (OMIM:128100). Biallelic variants cause a more severe phenotype of congenital arthrogryposis (OMIM:618947) and movement impairments including dystonia are also common (PMIDs: 29053766, 30244176). For this reason the MOI was updated from 'monoallelic' only to 'both mono- and biallelic (biallelic more severe)'.
Early onset dystonia v1.112 TOR1A Arina Puzriakova Mode of inheritance for gene: TOR1A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Early onset dystonia v1.111 JPH3_CTG Sarah Leigh commented on STR: JPH3_CTG
Early onset dystonia v1.111 ATXN3_CAG Eleanor Williams commented on STR: ATXN3_CAG
Early onset dystonia v1.111 ATXN2_CAG Ivone Leong commented on STR: ATXN2_CAG
Early onset dystonia v1.111 ATXN10_ATTCT Ivone Leong commented on STR: ATXN10_ATTCT
Early onset dystonia v1.111 JPH3_CTG Arina Puzriakova Classified STR: JPH3_CTG as Green List (high evidence)
Early onset dystonia v1.111 JPH3_CTG Arina Puzriakova Str: jph3_ctg has been classified as Green List (High Evidence).
Early onset dystonia v1.110 ATXN3_CAG Arina Puzriakova Classified STR: ATXN3_CAG as Green List (high evidence)
Early onset dystonia v1.110 ATXN3_CAG Arina Puzriakova Str: atxn3_cag has been classified as Green List (High Evidence).
Early onset dystonia v1.109 ATXN2_CAG Arina Puzriakova Classified STR: ATXN2_CAG as Green List (high evidence)
Early onset dystonia v1.109 ATXN2_CAG Arina Puzriakova Str: atxn2_cag has been classified as Green List (High Evidence).
Early onset dystonia v1.106 JPH3_CTG Arina Puzriakova Pathogenic Number of Repeats for JPH3_CTG was changed from 41 to 40.
Source NHS GMS was added to STR: JPH3_CTG.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Early onset dystonia v1.106 ATXN3_CAG Arina Puzriakova Normal Number of Repeats for ATXN3_CAG was changed from 44 to 45.
Source NHS GMS was added to STR: ATXN3_CAG.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Early onset dystonia v1.106 ATXN2_CAG Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32.
Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35.
Source NHS GMS was added to STR: ATXN2_CAG.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Early onset dystonia v1.106 ATXN10_ATTCT Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33.
Source NHS GMS was added to STR: ATXN10_ATTCT.
Early onset dystonia v1.105 SPATA5L1 Ivone Leong Classified gene: SPATA5L1 as Green List (high evidence)
Early onset dystonia v1.105 SPATA5L1 Ivone Leong Added comment: Comment on list classification: There is enough evidence for this gene to be Green.
Early onset dystonia v1.105 SPATA5L1 Ivone Leong Gene: spata5l1 has been classified as Green List (High Evidence).
Early onset dystonia v1.104 SPATA5L1 Ivone Leong Tag Q1_22_rating was removed from gene: SPATA5L1.
Early onset dystonia v1.104 SPATA5L1 Ivone Leong Entity copied from Intellectual disability v3.1495
Early onset dystonia v1.104 SPATA5L1 Ivone Leong gene: SPATA5L1 was added
gene: SPATA5L1 was added to Early onset dystonia. Sources: Literature,Expert Review Amber
Q1_22_rating tags were added to gene: SPATA5L1.
Mode of inheritance for gene: SPATA5L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5L1 were set to 34626583
Phenotypes for gene: SPATA5L1 were set to Neurodevelopmental disorder with hearing loss and spasticity, OMIM:619616
Early onset dystonia v1.103 SLC30A10 Arina Puzriakova Phenotypes for gene: SLC30A10 were changed from Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, andChronic Liver Disease; Hypermanganesemia with dystonia, polycythemia, and cirrhosis, 613280 to Hypermanganesemia with dystonia 1, OMIM:613280; Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease
Early onset dystonia v1.102 ACTB Sarah Leigh Classified gene: ACTB as Green List (high evidence)
Early onset dystonia v1.102 ACTB Sarah Leigh Added comment: Comment on list classification: Based on the green rating for this gene on https://panelapp.genomicsengland.co.uk/panels/847/gene/ACTB/ and review from Eldar Dedic.
Early onset dystonia v1.102 ACTB Sarah Leigh Gene: actb has been classified as Green List (High Evidence).
Early onset dystonia v1.101 ACTB Sarah Leigh Phenotypes for gene: ACTB were changed from Dystonia, juvenile-onset, 607371Baraitser-Winter syndrome 1, 243310 to Dystonia, juvenile-onset OMIM:607371; developmental malformations-deafness-dystonia syndrome MONDO:0011823; Baraitser-Winter syndrome 1 OMIM:243310; Baraitser-Winter syndrome 1 MONDO:0009470
Early onset dystonia v1.100 ACTB Sarah Leigh Publications for gene: ACTB were set to
Early onset dystonia v1.99 GCDH Eldar Dedic reviewed gene: GCDH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21912879, 33064266; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset dystonia v1.99 GAMT Eldar Dedic reviewed gene: GAMT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19027335, 33996490, 12557293, 19288536, 16855203; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset dystonia v1.99 FOXG1 Eldar Dedic changed review comment from: Dzinovic, et al. (2021, PMID: 34399161) analyzed 45 pediatric complex dystonia cases. The whole-exome-sequencing revealed de novo heterozygous FOXG1 c.703C >T (p.Leu235Phe) variant in 3 years of age female case of European ethnicity. Parents were Sanger sequenced.

- Please note that FOXG1 c.703C >T (p.Leu235Phe) variant was absent from gnomAD v2.1.1 as of December 2021

Wong, et al. (2019, PMID: 31316448) analyzed 30 cases with encephalopathy and movement impairments. Whole-exome-sequencing revealed 3 variants (c.763 T>C (p.Trp255Arg); c.250delC (p.Gln86Argfs*106); c.256dupC (p.Gln86Aspfs*34)) in FOXG1 gene in 3 Han Chinese cases (between 2 and 17 years of age) from Taiwan who had dystonia , respectively (Table 1).

- Please note that FOXG1 c.250delC (p.Gln86Argfs*106) variant was filtered from gnomAD v2.1.1, while FOXG1 c.763 T>C (p.Trp255Arg) and FOXG1 c.256dupC (p.Gln86Aspfs*34) variants were absent from gnomAD v2.1.1 as of December 2021

Mencarelli, et al. (2010, PMID: 19578037) analyzed 107 cases of European origin (including 60 Rett syndrome (RTT), 43 encephalopathy, and 4 RTT-like patients). The FOXG1 c.643T>C (p.Phe215Leu) variant has been found de novo in one 8 years of age female RTT patient with dystonia (diagnosed at 2 years of age) of French origin.

- Please note that FOXG1 c.643T>C (p.Phe215Leu) variant was absent from gnomAD v2.1.1 as of December 2021; to: Dzinovic, et al. (2021, PMID: 34399161) analyzed 45 pediatric complex dystonia cases. The whole-exome-sequencing revealed de novo heterozygous FOXG1 c.703C >T (p.Leu235Phe) variant in 3 years of age female case of European ethnicity. Parents were Sanger sequenced.

- Please note that FOXG1 c.703C >T (p.Leu235Phe) variant was absent from gnomAD v2.1.1 as of December 2021

Wong, et al. (2019, PMID: 31316448) analyzed 30 cases with encephalopathy and movement impairments. Whole-exome-sequencing revealed 3 variants (c.763 T>C (p.Trp255Arg); c.250delC (p.Gln86Argfs*106); c.256dupC (p.Gln86Aspfs*34)) in FOXG1 gene in 3 Han Chinese cases (between 2 and 17 years of age) from Taiwan who had dystonia, respectively (Table 1).

- Please note that FOXG1 c.250delC (p.Gln86Argfs*106) variant was filtered from gnomAD v2.1.1, while FOXG1 c.763 T>C (p.Trp255Arg) and FOXG1 c.256dupC (p.Gln86Aspfs*34) variants were absent from gnomAD v2.1.1 as of December 2021

Mencarelli, et al. (2010, PMID: 19578037) analyzed 107 cases of European origin (including 60 Rett syndrome (RTT), 43 encephalopathy, and 4 RTT-like patients). The FOXG1 c.643T>C (p.Phe215Leu) variant has been found de novo in one 8 years of age female RTT patient with dystonia (diagnosed at 2 years of age) of French origin.

- Please note that FOXG1 c.643T>C (p.Phe215Leu) variant was absent from gnomAD v2.1.1 as of December 2021
Early onset dystonia v1.99 FOXG1 Eldar Dedic reviewed gene: FOXG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34399161, 31316448, 19578037; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset dystonia v1.99 ARX Eldar Dedic reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31324350, 29778428, 23657928, 29343471; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset dystonia v1.99 ACTB Eldar Dedic reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 31970217, 29788902, 28849312, 27862284, 29220674, 25255767; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset dystonia v1.99 ACTB Eldar Dedic Deleted their review
Early onset dystonia v1.99 ACTB Eldar Dedic Deleted their comment
Early onset dystonia v1.99 AFG3L2 Eldar Dedic reviewed gene: AFG3L2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32219868; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset dystonia v1.99 ACTB Eldar Dedic changed review comment from: Freitas, et al. (2020, PMID 31970217) presented 52 years of age Brazilian female case with dystonia (onset at age of 25 years) who had additional clinical features (but without facial dysmorphism and brain abnormalities). Whole-exome-sequencing showed the presence of ACTB c.547C>T (p.Arg183Trp) variant. This variant was absent from gnomAD v2.1.1 as of December 2021.

Skogseid, et al. (2018, PMID 29788902) presented 23 years old female case with dystonia (age at onset 13 years), mild dysmorphic facial traits and additional clinical features (but with grossly maintained brain structure). Whole-exome-sequencing revealed heterozygous ACTB c.547C>T (p.Arg183Trp) variant. The case was negative for the aCGH analysis.

Zech, et al. (2017, PMID 28849312) presented 9 unrelated cases with combined and/or complex dystonia (8 of European and 1 of Asian origin). Whole-exome-sequencing revealed de novo ACTB c.547C>T (p.Arg183Trp) variant in 39-years-old Czech male case with complex dystonia (age of onset at 24 years) who had additional clinical features (but with normal brain MRI). The variant absence in parents has been confirmed through Sanger sequencing.

Eggink, et al. (2017, PMID 27862284) presented a family with dystonia. Whole-exome-sequencing revealed ACTB c.547C>T (p.Arg183Trp) variant in 2 family members: 22 years old female with dystonia (age of onset at 19 years) who in addition to other clinical features showed high-arched eyebrows (but with normal brain MRI results); her 49 years old mother with dystonia (who at age 16 experienced hands trembling, at age 21 she had writer’s cramp diagnosed) and additional clinical features.

Cuvertino, et al. (2017, PMID 29220674) analyzed data of more than 15,000 suspected genetic development disorder individuals, 26 cases with 7p22.1 deletions and 4,293 trios from the Deciphering Developmental Disorders study. The ACTB c.1097dupG (p.Ser368Leufs*13) variant has been found de novo in 12 years old heterozygous male case (of United Kingdom origin; Table S1) who had dystonia (as well as additional clinical features; Table 1). This variant was absent from gnomAD v2.1.1 as of December 2021.
(Please note that ACTB c.1097dupG (p.Ser368Leufs*13) results in extension of protein)

Hundt, et al. (2014, PMID 25255767) presented in vitro functional study on Sf9 cells. The results showed that ACTB c.547C>T (p.Arg183Trp) variant resulted in 3 times higher inhibition of DNase I-mediated nucleic acid cleavage (p < 0.0001; Fig.2A), unchanged thermal stability (Fig. 2B), nucleotide exchange from actin monomer was 2.4 times slower (p = 0.0113; Fig.3), 1.9 times faster half-time polymerization (p = 0.0006; Fig. 4A), 1.7 times higher ATP turnover (Fig. 4B), significantly reduced half-time of the depolymerization (Fig. 4C), close to normal binding to the profilin II (Fig. 5A), 4 times lower ability to activate ATPase of nonmuscle myosin-2A isoform (Fig. 6), in comparison to the wild-type. The authors also carried out the computational analysis and showed that this variant impaired the opening of the nucleotide cleft (Fig. 7C, Fig. 8B).; to: Freitas, et al. (2020, PMID: 31970217) presented 52 years of age Brazilian female case with dystonia (onset at age of 25 years) who had additional clinical features (but without facial dysmorphism and brain abnormalities). Whole-exome-sequencing showed the presence of ACTB c.547C>T (p.Arg183Trp) variant. This variant was absent from gnomAD v2.1.1 as of December 2021.

Skogseid, et al. (2018, PMID: 29788902) presented 23 years old female case with dystonia (age at onset 13 years), mild dysmorphic facial traits and additional clinical features (but with grossly maintained brain structure). Whole-exome-sequencing revealed heterozygous ACTB c.547C>T (p.Arg183Trp) variant. The case was negative for the aCGH analysis.

Zech, et al. (2017, PMID: 28849312) presented 9 unrelated cases with combined and/or complex dystonia (8 of European and 1 of Asian origin). Whole-exome-sequencing revealed de novo ACTB c.547C>T (p.Arg183Trp) variant in 39-years-old Czech male case with complex dystonia (age of onset at 24 years) who had additional clinical features (but with normal brain MRI). The variant absence in parents has been confirmed through Sanger sequencing.

Eggink, et al. (2017, PMID: 27862284) presented a family with dystonia. Whole-exome-sequencing revealed ACTB c.547C>T (p.Arg183Trp) variant in 2 family members: 22 years old female with dystonia (age of onset at 19 years) who in addition to other clinical features showed high-arched eyebrows (but with normal brain MRI results); her 49 years old mother with dystonia (who at age 16 experienced hands trembling, at age 21 she had writer’s cramp diagnosed) and additional clinical features.

Cuvertino, et al. (2017, PMID: 29220674) analyzed data of more than 15,000 suspected genetic development disorder individuals, 26 cases with 7p22.1 deletions and 4,293 trios from the Deciphering Developmental Disorders study. The ACTB c.1097dupG (p.Ser368Leufs*13) variant has been found de novo in 12 years old heterozygous male case (of United Kingdom origin; Table S1) who had dystonia (as well as additional clinical features; Table 1). This variant was absent from gnomAD v2.1.1 as of December 2021.
(Please note that ACTB c.1097dupG (p.Ser368Leufs*13) results in extension of protein)

Hundt, et al. (2014, PMID: 25255767) presented in vitro functional study on Sf9 cells. The results showed that ACTB c.547C>T (p.Arg183Trp) variant resulted in 3 times higher inhibition of DNase I-mediated nucleic acid cleavage (p < 0.0001; Fig.2A), unchanged thermal stability (Fig. 2B), nucleotide exchange from actin monomer was 2.4 times slower (p = 0.0113; Fig.3), 1.9 times faster half-time polymerization (p = 0.0006; Fig. 4A), 1.7 times higher ATP turnover (Fig. 4B), significantly reduced half-time of the depolymerization (Fig. 4C), close to normal binding to the profilin II (Fig. 5A), 4 times lower ability to activate ATPase of nonmuscle myosin-2A isoform (Fig. 6), in comparison to the wild-type. The authors also carried out the computational analysis and showed that this variant impaired the opening of the nucleotide cleft (Fig. 7C, Fig. 8B).
Early onset dystonia v1.99 ACTB Eldar Dedic reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31970217, 29788902, 28849312, 27862284, 29220674, 25255767; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset dystonia v1.99 ACTB Eldar Dedic Deleted their review
Early onset dystonia v1.99 ACTB Eldar Dedic reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: 31970217, 29788902, 28849312, 27862284, 29220674, 25255767; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset dystonia v1.99 RNASEH2B Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from Dystonia to Aicardi-Goutieres syndrome 2, OMIM:61018
Early onset dystonia v1.98 HPRT1 Arina Puzriakova Mode of inheritance for gene: HPRT1 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset dystonia v1.97 HPRT1 Arina Puzriakova Phenotypes for gene: HPRT1 were changed from Dystonia to Lesch-Nyhan syndrome, OMIM:300322; Dystonia
Early onset dystonia v1.96 JPH3_CTG Arina Puzriakova Phenotypes for STR: JPH3_CTG were changed from Huntington disease-like 2 606438 to Huntington disease-like 2, OMIM:606438
Early onset dystonia v1.95 CSTB Arina Puzriakova Phenotypes for gene: CSTB were changed from Epilepsy, progressive myoclonic 1A, 254800; microcephaly and severe dyskinesia (26843564) to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Early onset dystonia v1.94 CSTB Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB.
Early onset dystonia v1.94 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from Dystonia to Episodic ataxia, type 2, OMIM:108500
Early onset dystonia v1.93 CACNA1A Arina Puzriakova Mode of inheritance for gene: CACNA1A was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset dystonia v1.92 ATXN3_CAG Arina Puzriakova Phenotypes for STR: ATXN3_CAG were changed from Machado-Joseph disease 109150 to Machado-Joseph disease, OMIM:109150
Early onset dystonia v1.91 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090
Early onset dystonia v1.90 ATXN10_ATTCT Arina Puzriakova Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Early onset dystonia v1.89 SERAC1 Arina Puzriakova Phenotypes for gene: SERAC1 were changed from 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739; MEGDEL syndrome; 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome; MEGDHEL syndrome; Dystonia to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, OMIM:614739; Dystonia
Early onset dystonia v1.88 XK Ivone Leong Phenotypes for gene: XK were changed from McLeod syndrome with or without chronic granulomatous disease OMIM 300842 to McLeod syndrome with or without chronic granulomatous disease,OMIM:300842
Early onset dystonia v1.87 ATM Arina Puzriakova Phenotypes for gene: ATM were changed from Dystonia; Ataxia telangiectasia to Ataxia-telangiectasia, OMIM:208900
Early onset dystonia v1.86 ATXN10_ATTCT Arina Puzriakova Tag curated_removed tag was added to STR: ATXN10_ATTCT.
Early onset dystonia v1.86 TOR1A Arina Puzriakova Phenotypes for gene: TOR1A were changed from Early-Onset Primary Dystonia; Dystonia-1, torsion, 128100; Autosomal dominant or sporadic dystonia (DYT1) to Dystonia-1, torsion, OMIM:128100; Dystonic disorder, MONDO:0003441
Early onset dystonia v1.85 DDC Arina Puzriakova Phenotypes for gene: DDC were changed from Dystonia to Aromatic L-amino acid decarboxylase deficiency, OMIM:608643; Aromatic L-amino acid decarboxylase deficiency, MONDO:0012084; Floppy child; Dystonia; Hypotonia; Developmental delay; Oculogyric crisis
Early onset dystonia v1.84 DDC Arina Puzriakova Publications for gene: DDC were set to
Early onset dystonia v1.83 DDC Arina Puzriakova Mode of inheritance for gene: DDC was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset dystonia v1.82 DDC Arina Puzriakova Classified gene: DDC as Green List (high evidence)
Early onset dystonia v1.82 DDC Arina Puzriakova Added comment: Comment on list classification: Upgraded rating from Red to Green, in line with the review by Lothar Schlueter. Dystonia as a feature of the phenotype, most commonly arising in infancy. DDC is already Green on the GMS 'Childhood onset dystonia or chorea or related movement disorder' version 1.62 panel.
Early onset dystonia v1.82 DDC Arina Puzriakova Gene: ddc has been classified as Green List (High Evidence).
Early onset dystonia v1.81 DDC Lothar Schlueter reviewed gene: DDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 28100251, 30952622; Phenotypes: Aromatic L-amino acid decarboxylase deficiency 608643, floppy child, dystonia, hypotonia, developmental delay, oculogyric crisis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset dystonia v1.81 XK Louise Daugherty Classified gene: XK as Green List (high evidence)
Early onset dystonia v1.81 XK Louise Daugherty Gene: xk has been classified as Green List (High Evidence).
Early onset dystonia v1.80 XK Rachel Jones gene: XK was added
gene: XK was added to Early onset dystonia. Sources: Literature
Mode of inheritance for gene: XK was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: XK were set to 11761473; 11761473
Phenotypes for gene: XK were set to McLeod syndrome with or without chronic granulomatous disease OMIM 300842
Penetrance for gene: XK were set to Incomplete
Review for gene: XK was set to GREEN
gene: XK was marked as current diagnostic
Added comment: Several publications including those given above regarding this well characterised link between XK gene and McLeod syndrome in many patients. Phenotype is acanthosis, haemolysis and elevated CK. Neurological phenotype (from OMIM) "Onset of neurologic symptoms ranges between 25 and 60 years (mean onset 30-40 years), and penetrance appears to be high. Additional symptoms include generalized seizures, neuromuscular symptoms leading to weakness and atrophy, and cardiomyopathy mainly manifesting with atrial fibrillation, malignant arrhythmias, and dilated cardiomyopathy"

Testing not currently offered by UK labs but several accredited European laboratories are offering testing.
Sources: Literature
Early onset dystonia v1.78 CYP27A1 Philip Dawson reviewed gene: CYP27A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30054180, 29484516; Phenotypes: Cerebrotendinous xanthomatosis, 213700, Dystonia, including childhood & adult onset.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset dystonia v1.78 CP Louise Daugherty Phenotypes for gene: CP were changed from Dystonia; Aceruloplasminemia to Dystonia; Aceruloplasminemia; Cerebellar ataxia, 604290; Hemosiderosis, systemic, due to aceruloplasminemia, 604290
Early onset dystonia v1.77 WDR73 Louise Daugherty Phenotypes for gene: WDR73 were changed from Galloway Mowat Syndrome to Galloway-Mowat syndrome 1, 251300
Early onset dystonia v1.76 BCAP31 Eleanor Williams Phenotypes for gene: BCAP31 were changed from Deafness, dystonia and cerebellar hypomyelination, 300475 to Deafness, dystonia and cerebellar hypomyelination, 300475; DEAFNESS, DYSTONIA, AND CENTRAL HYPOMYELINATION WITH DISORGANIZATION OF THE GOLGI APPARATUS
Early onset dystonia v1.75 BCAP31 Eleanor Williams Publications for gene: BCAP31 were set to
Early onset dystonia v1.74 BCAP31 Eleanor Williams Mode of inheritance for gene: BCAP31 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset dystonia v1.73 BCAP31 Eleanor Williams Classified gene: BCAP31 as Green List (high evidence)
Early onset dystonia v1.73 BCAP31 Eleanor Williams Added comment: Comment on list classification: More than 3 cases with variants in BCAP31 and a dystonia phenotype
Early onset dystonia v1.73 BCAP31 Eleanor Williams Gene: bcap31 has been classified as Green List (High Evidence).
Early onset dystonia v1.72 BCAP31 Eleanor Williams commented on gene: BCAP31
Early onset dystonia v1.72 DLAT Eleanor Williams Phenotypes for gene: DLAT were changed from Dystonia to episodic dystonia; pyruvate dehydrogenase deficiency; Pyruvate dehydrogenase E2 deficiency
Early onset dystonia v1.71 DLAT Eleanor Williams Publications for gene: DLAT were set to
Early onset dystonia v1.70 DLAT Eleanor Williams Mode of inheritance for gene: DLAT was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset dystonia v1.69 DLAT Eleanor Williams Classified gene: DLAT as Green List (high evidence)
Early onset dystonia v1.69 DLAT Eleanor Williams Added comment: Comment on list classification: 3 unrelated cases with plausible disease causing variants in the DLAT gene. All cases show dystonia in childhood.
Early onset dystonia v1.69 DLAT Eleanor Williams Gene: dlat has been classified as Green List (High Evidence).
Early onset dystonia v1.68 DLAT Eleanor Williams commented on gene: DLAT
Early onset dystonia v1.68 DLAT Chris Buxton reviewed gene: DLAT: Rating: AMBER; Mode of pathogenicity: None; Publications: 20022530, 16049940; Phenotypes: episodic dystonia, pyruvate dehydrogenase deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset dystonia v1.68 BCAP31 Chris Buxton reviewed gene: BCAP31: Rating: RED; Mode of pathogenicity: None; Publications: 24011989; Phenotypes: Intellectual disability, dystonia, sensorineural deafness; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset dystonia v1.68 ATXN3_CAG Louise Daugherty Phenotypes for STR: ATXN3_CAG were changed from Machado-Joseph disease 109150 to Machado-Joseph disease 109150
Early onset dystonia v1.67 ATXN2_CAG Louise Daugherty Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to Spinocerebellar ataxia 2 183090
Early onset dystonia v1.66 ATXN10_ATTCT Louise Daugherty Phenotypes for STR: ATXN10_ATTCT were changed from to Spinocerebellar ataxia 10 603516
Early onset dystonia v1.65 JPH3_CTG Arianna Tucci Phenotypes for STR: JPH3_CTG were changed from to Huntington disease-like 2 606438
Early onset dystonia v1.64 ATXN3_CAG Arianna Tucci Phenotypes for STR: ATXN3_CAG were changed from to Machado-Joseph disease 109150
Early onset dystonia v1.63 ATXN2_CAG Arianna Tucci Phenotypes for STR: ATXN2_CAG were changed from to Spinocerebellar ataxia 2 183090
Early onset dystonia v1.62 JPH3_CTG Arianna Tucci Repeated Sequence for JPH3_CTG was changed from CAG to CTG.
Early onset dystonia v1.61 JPH3_CTG Louise Daugherty Repeated Sequence for JPH3_CTG was changed from CTG to CAG.
Early onset dystonia v1.60 JPH3_CTG Louise Daugherty Deleted their comment
Early onset dystonia v1.60 JPH3_CTG Louise Daugherty commented on STR: JPH3_CTG
Early onset dystonia v1.60 JPH3_CTG Louise Daugherty Repeated Sequence for JPH3_CTG was changed from CAG to CTG.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Early onset dystonia v1.59 JPH3_CTG Louise Daugherty Tag STR tag was added to STR: JPH3_CTG.
Early onset dystonia v1.59 ATXN3_CAG Louise Daugherty Tag STR tag was added to STR: ATXN3_CAG.
Early onset dystonia v1.59 ATXN2_CAG Louise Daugherty Tag STR tag was added to STR: ATXN2_CAG.
Early onset dystonia v1.59 ATXN10_ATTCT Louise Daugherty Classified STR: ATXN10_ATTCT as No list
Early onset dystonia v1.59 ATXN10_ATTCT Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Early onset dystonia v1.59 ATXN10_ATTCT Louise Daugherty Str: atxn10_attct has been removed from the panel.
Early onset dystonia v1.58 ATXN10_ATTCT Louise Daugherty Tag STR tag was added to STR: ATXN10_ATTCT.
Early onset dystonia v1.58 ATXN10_ATTCT Arianna Tucci Marked STR: ATXN10_ATTCT as ready
Early onset dystonia v1.58 ATXN10_ATTCT Arianna Tucci Str: atxn10_attct has been classified as Red List (Low Evidence).
Early onset dystonia v1.58 ATXN10_ATTCT Arianna Tucci Classified STR: ATXN10_ATTCT as Red List (low evidence)
Early onset dystonia v1.58 ATXN10_ATTCT Arianna Tucci Str: atxn10_attct has been classified as Red List (Low Evidence).
Early onset dystonia v1.57 ATXN10_ATTCT Arianna Tucci Marked STR: ATXN10_ATTCT as ready
Early onset dystonia v1.57 ATXN10_ATTCT Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Early onset dystonia v1.57 ATXN10_ATTCT Arianna Tucci Str: atxn10_attct has been classified as Green List (High Evidence).
Early onset dystonia v1.57 ATXN10_ATTCT Arianna Tucci Classified STR: ATXN10_ATTCT as Green List (high evidence)
Early onset dystonia v1.57 ATXN10_ATTCT Arianna Tucci Str: atxn10_attct has been classified as Green List (High Evidence).
Early onset dystonia v1.56 ATXN10_ATTCT Arianna Tucci STR: ATXN10_ATTCT was added
STR: ATXN10_ATTCT was added to Early onset dystonia. Sources: Expert Review
Mode of inheritance for STR: ATXN10_ATTCT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Early onset dystonia v1.55 ATXN3_CAG Arianna Tucci Marked STR: ATXN3_CAG as ready
Early onset dystonia v1.55 ATXN3_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Early onset dystonia v1.55 ATXN3_CAG Arianna Tucci Str: atxn3_cag has been classified as Green List (High Evidence).
Early onset dystonia v1.55 ATXN3_CAG Arianna Tucci Classified STR: ATXN3_CAG as Green List (high evidence)
Early onset dystonia v1.55 ATXN3_CAG Arianna Tucci Str: atxn3_cag has been classified as Green List (High Evidence).
Early onset dystonia v1.54 ATXN3_CAG Arianna Tucci STR: ATXN3_CAG was added
STR: ATXN3_CAG was added to Early onset dystonia. Sources: Expert Review
Mode of inheritance for STR: ATXN3_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: ATXN3_CAG was set to GREEN
STR: ATXN3_CAG was marked as current diagnostic
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Early onset dystonia v1.53 ATXN2_CAG Arianna Tucci Marked STR: ATXN2_CAG as ready
Early onset dystonia v1.53 ATXN2_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Early onset dystonia v1.53 ATXN2_CAG Arianna Tucci Str: atxn2_cag has been classified as Green List (High Evidence).
Early onset dystonia v1.53 ATXN2_CAG Arianna Tucci Classified STR: ATXN2_CAG as Green List (high evidence)
Early onset dystonia v1.53 ATXN2_CAG Arianna Tucci Str: atxn2_cag has been classified as Green List (High Evidence).
Early onset dystonia v1.52 ATXN2_CAG Arianna Tucci STR: ATXN2_CAG was added
STR: ATXN2_CAG was added to Early onset dystonia. Sources: Expert Review
Mode of inheritance for STR: ATXN2_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: ATXN2_CAG was set to GREEN
STR: ATXN2_CAG was marked as current diagnostic
Added comment: Sources: Expert Review
Early onset dystonia v1.51 JPH3_CTG Arianna Tucci Marked STR: JPH3_CTG as ready
Early onset dystonia v1.51 JPH3_CTG Arianna Tucci Added comment: Comment when marking as ready: Added to the panel following the Webex discussion with GMC experts (6/09/2018) about feeding back STR results
Early onset dystonia v1.51 JPH3_CTG Arianna Tucci Str: jph3_ctg has been classified as Green List (High Evidence).
Early onset dystonia v1.51 JPH3_CTG Arianna Tucci Classified STR: JPH3_CTG as Green List (high evidence)
Early onset dystonia v1.51 JPH3_CTG Arianna Tucci Str: jph3_ctg has been classified as Green List (High Evidence).
Early onset dystonia v1.50 JPH3_CTG Arianna Tucci STR: JPH3_CTG was added
STR: JPH3_CTG was added to Early onset dystonia. Sources: Expert Review
Mode of inheritance for STR: JPH3_CTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: JPH3_CTG was set to GREEN
Added comment: Added to the panel following the Webex discussion with GMC experts (6/09/2018) about feeding back STR results
Sources: Expert Review
Early onset dystonia v1.49 HPCA Rebecca Foulger Classified gene: HPCA as Green List (high evidence)
Early onset dystonia v1.49 HPCA Rebecca Foulger Added comment: Comment on list classification: Updated rating from Grey to Green: Gene added to panel by Zornitza Stark. 1 Green expert review (by Zornitza) plus 4 unrelated cases in literature supporting variants in HPCA causing AR dystonia. Note that HPCA variants are a rare cause of AR dystonia.
Early onset dystonia v1.49 HPCA Rebecca Foulger Gene: hpca has been classified as Green List (High Evidence).
Early onset dystonia v1.48 HPCA Rebecca Foulger commented on gene: HPCA: Although two independent studies (PMID:27771228 and PMID:27145302) from 2017 and 2016 failed to support the role of HPCA in pathogenesis of dystonia, this is most likely because HPCA variants represent a rare form of dystonia.
Early onset dystonia v1.48 HPCA Rebecca Foulger commented on gene: HPCA: Atasu et al. 2018 (PMID:30145809) revealed two unlreated consanguineous Turkish families with complex dystonia and novel HPCA variants (p.W103* and p.P10PfsTer80). The first family started to suffer involuntary head movements at age 8 months, and official examination at age 20 revealed dystonia. The second family developed dystonia of lower limbs age 17.
Early onset dystonia v1.48 HPCA Rebecca Foulger commented on gene: HPCA: In 3 siblings (age 61, 57 and 51) from consanguineous Sephardic Hewish family with dystonia (MIM:224500) which presented in their first decade, Charlesworth et al, 2015 (PMID:25799108) identified a homozygous missense variant in HPCA (N75K). Sequencing of HPCA in samples from 150 additional patients with early-onset dystonia (<30 years old) identified compound heterozygous missense variants (T71N and A190T) in a 64 year old woman of Sri Lankan origin with the disorder. The woman reported dystonia onset in her late-teens to early twenties. Her unaffected siblings contained one or both wild-type alleles supporting pathogenicity of the compound heterozygous variants in the affected individual.
Early onset dystonia v1.48 HPCA Rebecca Foulger Phenotypes for gene: HPCA were changed from Dystonia 2, torsion, autosomal recessive, MIM#224500 to Dystonia 2, torsion, autosomal recessive, 224500; childhood-onset generalized dystonia; adolescence-onset segmental dystonia; generalized dystonia with additional neurological features
Early onset dystonia v1.47 HPCA Rebecca Foulger Added comment: Comment on mode of inheritance: Biallelic mode of inheritance supported by literature (PMID:25799108), and OMIM.
Early onset dystonia v1.47 HPCA Rebecca Foulger Mode of inheritance for gene: HPCA was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Early onset dystonia HPCA Zornitza Stark Added gene to panel
Early onset dystonia NDUFA12 Sarah Leigh Added gene to panel
Early onset dystonia SERAC1 Louise Daugherty classified SERAC1 as Green List (high evidence)
Early onset dystonia SERAC1 Louise Daugherty edited their review of SERAC1
Early onset dystonia SERAC1 Louise Daugherty reviewed SERAC1
Early onset dystonia PCDH12 Ellen McDonagh edited their review of PCDH12
Early onset dystonia PCDH12 Ellen McDonagh reviewed PCDH12
Early onset dystonia PCDH12 Ellen McDonagh Added gene to panel
Early onset dystonia HTRA2 Sarah Leigh classified HTRA2 as green
Early onset dystonia HTRA2 Sarah Leigh added HTRA2 to panel
Early onset dystonia HTRA2 Sarah Leigh reviewed HTRA2
Early onset dystonia GNAO1 Rebecca Foulger classified GNAO1 as green
Early onset dystonia GNAO1 Rebecca Foulger commented on GNAO1
Early onset dystonia GNAO1 Rebecca Foulger added GNAO1 to panel
Early onset dystonia GNAO1 Rebecca Foulger reviewed GNAO1
Early onset dystonia NKX6-2 Sarah Leigh classified NKX6-2 as green
Early onset dystonia NKX6-2 Sarah Leigh added NKX6-2 to panel
Early onset dystonia NKX6-2 Sarah Leigh reviewed NKX6-2
Early onset dystonia YY1 Sarah Leigh classified YY1 as green
Early onset dystonia YY1 Sarah Leigh added YY1 to panel
Early onset dystonia YY1 Sarah Leigh reviewed YY1
Early onset dystonia ADAR Arianna Tucci classified ADAR as green
Early onset dystonia ADAR Arianna Tucci reviewed ADAR
Early onset dystonia CSTB Arianna Tucci classified CSTB as green
Early onset dystonia CSTB Arianna Tucci added CSTB to panel
Early onset dystonia CSTB Arianna Tucci reviewed CSTB
Early onset dystonia ADCY5 Arianna Tucci classified ADCY5 as green
Early onset dystonia ADCY5 Arianna Tucci added ADCY5 to panel
Early onset dystonia ADCY5 Arianna Tucci reviewed ADCY5
Early onset dystonia PARK2 Louise Daugherty commented on PARK2
Early onset dystonia VAC14 Sarah Leigh classified VAC14 as green
Early onset dystonia VAC14 Sarah Leigh added VAC14 to panel
Early onset dystonia VAC14 Sarah Leigh reviewed VAC14
Early onset dystonia SLC39A14 Sarah Leigh added SLC39A14 to panel
Early onset dystonia SLC39A14 Sarah Leigh reviewed SLC39A14
Early onset dystonia MECR Sarah Leigh classified MECR as green
Early onset dystonia MECR Sarah Leigh added MECR to panel
Early onset dystonia MECR Sarah Leigh reviewed MECR
Early onset dystonia KMT2B Ellen McDonagh classified KMT2B as green
Early onset dystonia KMT2B Ellen McDonagh edited their review of KMT2B
Early onset dystonia KMT2B Ellen McDonagh commented on KMT2B
Early onset dystonia KMT2B Ellen McDonagh added KMT2B to panel
Early onset dystonia KMT2B Ellen McDonagh reviewed KMT2B
Early onset dystonia VPS13A Ellen McDonagh classified VPS13A as green
Early onset dystonia VPS13A Ellen McDonagh commented on VPS13A
Early onset dystonia SYNJ1 Ellen McDonagh classified SYNJ1 as green
Early onset dystonia SYNJ1 Ellen McDonagh commented on SYNJ1
Early onset dystonia PRKRA Ellen McDonagh commented on PRKRA
Early onset dystonia PRKRA Ellen McDonagh classified PRKRA as green
Early onset dystonia VPS13A Arianna Tucci reviewed VPS13A
Early onset dystonia TUBB4A Arianna Tucci reviewed TUBB4A
Early onset dystonia TOR1A Arianna Tucci reviewed TOR1A
Early onset dystonia THAP1 Arianna Tucci reviewed THAP1
Early onset dystonia TAF1 Arianna Tucci reviewed TAF1
Early onset dystonia SYNJ1 Arianna Tucci reviewed SYNJ1
Early onset dystonia SLC30A10 Arianna Tucci reviewed SLC30A10
Early onset dystonia SGCE Arianna Tucci reviewed SGCE
Early onset dystonia PRKRA Arianna Tucci reviewed PRKRA
Early onset dystonia GNAL Arianna Tucci reviewed GNAL
Early onset dystonia SPR Arianna Tucci reviewed SPR
Early onset dystonia ATP1A3 Arianna Tucci reviewed ATP1A3
Early onset dystonia ANO3 Arianna Tucci reviewed ANO3
Early onset dystonia GNAL Ellen McDonagh commented on GNAL
Early onset dystonia SPR Ellen McDonagh commented on SPR
Early onset dystonia PRKRA Ellen McDonagh edited their review of PRKRA
Early onset dystonia PRKRA Ellen McDonagh edited their review of PRKRA
Early onset dystonia Ellen McDonagh promoted panel to version 1
Early onset dystonia ATM Ellen Thomas marked ATM as ready
Early onset dystonia ATM Ellen Thomas classified ATM as green
Early onset dystonia ATM Ellen Thomas commented on ATM
Early onset dystonia APTX Ellen Thomas marked APTX as ready
Early onset dystonia APTX Ellen Thomas classified APTX as green
Early onset dystonia APTX Ellen Thomas commented on APTX
Early onset dystonia PNKD Ellen McDonagh marked PNKD as ready
Early onset dystonia PNKD Ellen McDonagh marked PNKD as ready
Early onset dystonia DCTN1 Ellen McDonagh marked DCTN1 as ready
Early onset dystonia DCTN1 Ellen McDonagh classified DCTN1 as red
Early onset dystonia TUBB4A Ellen McDonagh marked TUBB4A as ready
Early onset dystonia TUBB4A Ellen McDonagh classified TUBB4A as green
Early onset dystonia PINK1 Ellen McDonagh marked PINK1 as ready
Early onset dystonia PINK1 Ellen McDonagh classified PINK1 as green
Early onset dystonia PARK7 Ellen McDonagh marked PARK7 as ready
Early onset dystonia PARK7 Ellen McDonagh classified PARK7 as red
Early onset dystonia DCAF17 Ellen McDonagh marked DCAF17 as ready
Early onset dystonia DCAF17 Ellen McDonagh classified DCAF17 as green
Early onset dystonia CP Ellen McDonagh marked CP as ready
Early onset dystonia COASY Ellen McDonagh marked COASY as ready
Early onset dystonia COASY Ellen McDonagh classified COASY as green
Early onset dystonia ANO3 Ellen McDonagh marked ANO3 as ready
Early onset dystonia ANO3 Ellen McDonagh classified ANO3 as green
Early onset dystonia WDR45 Ellen McDonagh marked WDR45 as ready
Early onset dystonia TUBB4A Ellen McDonagh classified TUBB4A as amber
Early onset dystonia TOR1A Ellen McDonagh commented on TOR1A
Early onset dystonia THAP1 Ellen McDonagh classified THAP1 as green
Early onset dystonia TH Ellen McDonagh classified TH as green
Early onset dystonia SPR Ellen McDonagh classified SPR as green
Early onset dystonia SLC6A3 Ellen McDonagh classified SLC6A3 as green
Early onset dystonia SLC30A10 Ellen McDonagh marked SLC30A10 as ready
Early onset dystonia SLC30A10 Ellen McDonagh classified SLC30A10 as green
Early onset dystonia SLC2A1 Ellen McDonagh marked SLC2A1 as ready
Early onset dystonia SLC2A1 Ellen McDonagh classified SLC2A1 as green
Early onset dystonia SGCE Ellen McDonagh marked SGCE as ready
Early onset dystonia SGCE Ellen McDonagh classified SGCE as green
Early onset dystonia PRRT2 Ellen McDonagh marked PRRT2 as ready
Early onset dystonia PRRT2 Ellen McDonagh classified PRRT2 as green
Early onset dystonia PNKD Ellen McDonagh classified PNKD as green
Early onset dystonia PLA2G6 Ellen McDonagh marked PLA2G6 as ready
Early onset dystonia PLA2G6 Ellen McDonagh classified PLA2G6 as green
Early onset dystonia PINK1 Ellen McDonagh classified PINK1 as green
Early onset dystonia PARK7 Ellen McDonagh classified PARK7 as green
Early onset dystonia PARK2 Ellen McDonagh marked PARK2 as ready
Early onset dystonia PARK2 Ellen McDonagh classified PARK2 as green
Early onset dystonia PANK2 Ellen McDonagh marked PANK2 as ready
Early onset dystonia PANK2 Ellen McDonagh classified PANK2 as green
Early onset dystonia GCH1 Ellen McDonagh classified GCH1 as green
Early onset dystonia FTL Ellen McDonagh marked FTL as ready
Early onset dystonia FTL Ellen McDonagh classified FTL as green
Early onset dystonia FBXO7 Ellen McDonagh marked FBXO7 as ready
Early onset dystonia FBXO7 Ellen McDonagh classified FBXO7 as green
Early onset dystonia FA2H Ellen McDonagh marked FA2H as ready
Early onset dystonia FA2H Ellen McDonagh classified FA2H as green
Early onset dystonia FA2H Ellen McDonagh classified FA2H as green
Early onset dystonia DCAF17 Ellen McDonagh marked DCAF17 as ready
Early onset dystonia DCAF17 Ellen McDonagh classified DCAF17 as green
Early onset dystonia COASY Ellen McDonagh classified COASY as green
Early onset dystonia C19orf12 Ellen McDonagh marked C19orf12 as ready
Early onset dystonia C19orf12 Ellen McDonagh classified C19orf12 as green
Early onset dystonia ATP7B Ellen McDonagh marked ATP7B as ready
Early onset dystonia ATP1A3 Ellen McDonagh classified ATP1A3 as green
Early onset dystonia ATP13A2 Ellen McDonagh marked ATP13A2 as ready
Early onset dystonia ANO3 Ellen McDonagh classified ANO3 as amber
Early onset dystonia CHMP2B Ellen McDonagh marked CHMP2B as ready
Early onset dystonia CHMP2B Ellen McDonagh classified CHMP2B as green
Early onset dystonia WDR73 emma baple marked WDR73 as ready
Early onset dystonia WDR73 emma baple commented on WDR73
Early onset dystonia WDR73 emma baple classified WDR73 as green
Early onset dystonia WDR73 Ellen McDonagh added WDR73 to panel
Early onset dystonia WDR73 Ellen McDonagh reviewed WDR73
Early onset dystonia GNAL Ellen McDonagh marked GNAL as ready