Hereditary ataxia with onset in adulthood
Gene: FMR1
Pre-mutation associated with FX-TASCreated: 27 Apr 2019, 7:39 p.m.
Downgraded Green to Red. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene RedCreated: 1 Aug 2019, 3:43 p.m. | Last Modified: 1 Aug 2019, 3:43 p.m.
Panel Version: 1.188
Review and rating submitted by James Polke (Neurogenetics Laboratory, Institute of Neurology, London) on behalf of London North GLH for GMS Neurology specialist test group
Created: 27 Apr 2019, 8:55 p.m.
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.Created: 15 Apr 2019, 10:21 a.m.
Premutation range of the CGG repeat. Would not be expected to be associated with LoF FMR1 variants (c.f. Fragile X syndrome)Created: 15 Apr 2019, 10:06 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Fragile X tremor/ataxia syndrome
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: FMR1 were changed from FragileXtremor/ataxiasyndrome,300623; Fragile X tremor/ataxia syndrome; FMR1-related disorders include fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS), and FMR1-related premature ovarian insufficiency (POI); males with a tremor phenotype to Fragile X tremor/ataxia syndrome, OMIM:300623
Source Expert Review Red was added to FMR1. Rating Changed from Green List (high evidence) to Red List (low evidence)
Source London North GMS was added to FMR1.
Added phenotypes Fragile X tremor/ataxia syndrome for gene: FMR1
Source NHS GMS was added to FMR1.
Source Wessex and West Midlands GLH was added to FMR1.
Checked panel against panel constituents. Ready to promote to version 1.
Tag nucleotide-repeat-expansion tag was added to gene: FMR1.
gene: FMR1 was added gene: FMR1 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Green Mode of inheritance for gene: FMR1 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 gene: FMR1 were set to FragileXtremor/ataxiasyndrome,300623; males with a tremor phenotype; FMR1-related disorders include fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS), and FMR1-related premature ovarian insufficiency (POI)