Hereditary ataxia with onset in adulthood

Gene: TMEM106B

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 9 Mar 2022, 4:49 p.m. | Last Modified: 9 Mar 2022, 4:49 p.m.

Panel Version: 2.141

I don't know

Comment on list classification: This gene has been flagged for review at the next GMS panel update (added 'for-review tag) as there is only enough evidence for TMEM106B to be rated AMBER on this panel.

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 could be reviewed if evidence emerges of a more prominent ataxic phenotype.

Created: 12 Nov 2020, 5:21 p.m. | Last Modified: 12 Nov 2020, 5:21 p.m.

Panel Version: 2.16

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, 5:19 p.m. | Last Modified: 12 Nov 2020, 5:19 p.m.

Panel Version: 2.15

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

I don't know

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.

Green List (high evidence)

Multiple cases reported in the two papers all associated with a single recurrent de novo variant c.754G>A p.(Asp252Asn)

Created: 15 Apr 2019, 10:06 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hypomyelinating leukodystrophy 16, 617964

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