Hereditary ataxia with onset in adulthood

Gene: TUBA4A

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 6:10 p.m. | Last Modified: 24 Feb 2025, 6:10 p.m.

Panel Version: 7.10

At least 15 TUBA4A variants have been associated with Amyotrophic lateral sclerosis 22 with or without frontotemporal dementia, (OMIM:616208)(PMID: 25374358; 37418012; 38884572). Spastic ataxia (in 4/13 unrelated cases) and nystagmus (in 5/13 unrelated cases) have been noted as additional phenotypic features in patients reported by PMID: 37418012; 38884572. Furthermore, functional studies show that missense TUBA4A variants significantly alter the microtubule organization and dynamics, diminishing its repolymerization capability (PMID: 25374358; 38884572).

Created: 24 Sep 2024, 3:33 p.m. | Last Modified: 24 Sep 2024, 4:29 p.m.

Panel Version: 6.5

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Heterozygous missense TUBA4A variants (p.Pro173Ser, p.Pro173Arg, and p.Glu415Lys) recently reported to be associated with ataxia and spasticity in 24 individuals from 13 families in PMID: 37418012 and 38884572
Sources: Literature

Created: 20 Sep 2024, 3:26 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Ataxia; Spasticity; Nystagmus; Abnormal eye movements; Dysarthria; cognitive decline

Publications

• PMID: 37418012
• 38884572