Adult onset neurodegenerative disorder
Gene: CACNA1AComment on mode of inheritance: CACNA1A is associated with several phenotypes including SCA6 (OMIM:183086), episodic ataxia (OMIM:108500), familial hemiplegic migraine with or without ataxia (OMIM:141500), or developmental and epileptic encephalopathy (OMIM:617106). SCA6 is the only condition that may align with this panel; however, it is caused by nucleotide repeat expansions and there is a lack of relevance for SNVs.Created: 8 Nov 2021, 2:18 p.m. | Last Modified: 8 Nov 2021, 2:18 p.m.
Panel Version: 2.223
SCA6 - late-onset progressive cerebellar ataxia with onset of gait difficulties at age 50, as well as other variable phenotypes. >3 cases, SCA6 - STR mutation. , eg EIEE42, EA2, FHM1. In approximately 20% of cases of FHM, the disease is associated with a mild permanent cerebellar ataxia which may be progressive (PCA) - 10 unrelated cases had the same T666M variant. oTher variants also reported. Episodic ataxia is a genetically heterogeneous neurologic condition characterized by spells of incoordination and imbalance, often associated with progressive ataxia - LOF variants. Several casesCreated: 2 Sep 2019, 4:06 p.m. | Last Modified: 2 Sep 2019, 4:06 p.m.
Panel Version: 1.99
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
episodic ataxia type 2 (EA2),108500; familial hemiplegic migraine type 1, 141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia; Dystonia; Spinocerebellar ataxia 6; Episodic ataxia, type 2
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
episodic ataxia type 2 (EA2),108500; familial hemiplegic migraine type 1, 141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia; Dystonia; Spinocerebellar ataxia 6; Episodic ataxia, type 2
As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene RedCreated: 20 Sep 2019, 4:19 p.m. | Last Modified: 20 Sep 2019, 4:19 p.m.
Panel Version: 1.106
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.Created: 2 Sep 2019, 4:46 p.m. | Last Modified: 2 Sep 2019, 4:46 p.m.
Panel Version: 1.101
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
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.
Mode of inheritance for gene: CACNA1A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Tag treatable was removed from gene: CACNA1A. Tag currently-ngs-unreportable tag was added to gene: CACNA1A.
Phenotypes for gene: CACNA1A were changed from episodic ataxia type 2 (EA2),108500; familial hemiplegic migraine type 1, 141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia; Dystonia; Spinocerebellar ataxia 6; Episodic ataxia, type 2 to Spinocerebellar ataxia 6, OMIM:183086
Source Expert Review Red was added to CACNA1A. Rating Changed from Green List (high evidence) to Red List (low evidence)
Source Wessex and West Midlands GLH was added to CACNA1A.
Source Yorkshire and North East GLH was added to CACNA1A.
Source NHS GMS was added to CACNA1A.
Source London North GLH was added to CACNA1A.
Louise Daugherty: Comment on phenotypes: amended
Tag treatable tag was added to gene: CACNA1A.
Tag nucleotide-repeat-expansion tag was added to gene: CACNA1A.
Added phenotypes Dystonia for gene: CACNA1A
Added phenotypes episodic ataxia type 2 (EA2),108500; familial hemiplegic migraine type 1, 141500 for gene: CACNA1A
gene: CACNA1A was added gene: CACNA1A was added to Neurodegenerative disorders - adult onset. Sources: Expert Review Green Mode of inheritance for gene: CACNA1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CACNA1A were set to 21734179; 17575281 Phenotypes for gene: CACNA1A were set to Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia; Spinocerebellar ataxia 6; Episodic ataxia, type 2