Ataxia and cerebellar anomalies - narrow panel

Gene: TMEM106B

I don't know

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

• 29186371
• 29444210
• 30643851
• 32595021

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Green List (high evidence)

Cerebellar signs including ataxia prominent.
Sources: Expert list

Created: 13 Sep 2020, 7:26 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Leukodystrophy, hypomyelinating, 16, MIM# 617964

Publications

• 29186371
• 29444210

Variants in this GENE are reported as part of current diagnostic practice