Ataxia and cerebellar anomalies - narrow panel
Gene: TMEM106B
Comment on list classification: Rating Amber as only 2/6 cases present ataxia, which is mild in one individual. Cases are more likely to be recognised for the leukodystrophy feature of this disease presentation; however, this may be reviewed if evidence emerges of a more prominent ataxic phenotype.Created: 12 Nov 2020, 5:16 p.m. | Last Modified: 12 Nov 2020, 5:16 p.m.
Panel Version: 2.25
Associated with relevant phenotype in OMIM, and is a 'probable' gene for 'TMEM106B related hypomyelinating leukodystrophy' in Gene2Phenotype.
Recurrent variant c.754G>A p.(Asp252Asn) identified in 6 unrelated families from different ethnicities. Clinical characteristics include hypomyelinating leukodystrophy (6/6), nystagmus (6/6), hypotonia (5/6), cognitive impairment (5/6), movement disorder (3/6) and seizures (2/6).
Only 2 individuals present gait ataxia and intention tremor (mild/minimal in one case), with only mild cerebellar atrophy identified in one patient on brain MRI.Created: 12 Nov 2020, 5:07 p.m. | Last Modified: 12 Nov 2020, 5:09 p.m.
Panel Version: 2.24
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Leukodystrophy, hypomyelinating, 16 OMIM:617964
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Cerebellar signs including ataxia prominent.
Sources: Expert listCreated: 13 Sep 2020, 7:26 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Leukodystrophy, hypomyelinating, 16, MIM# 617964
Publications
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: TMEM106B were changed from Leukodystrophy, hypomyelinating, 16, MIM# 617964 to Leukodystrophy, hypomyelinating, 16, OMIM:617964; Leukodystrophy, hypomyelinating, 16, MONDO:0054791
Tag missense tag was added to gene: TMEM106B.
Mode of pathogenicity for gene: TMEM106B was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Publications for gene: TMEM106B were set to 29186371; 29444210
Gene: tmem106b has been classified as Amber List (Moderate Evidence).
gene: TMEM106B was added gene: TMEM106B was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list Mode of inheritance for gene: TMEM106B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TMEM106B were set to 29186371; 29444210 Phenotypes for gene: TMEM106B were set to Leukodystrophy, hypomyelinating, 16, MIM# 617964 Review for gene: TMEM106B was set to GREEN gene: TMEM106B was marked as current diagnostic