Hereditary ataxia with onset in adulthood

Gene: FAT2

Green List (high evidence)

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

Created: 11 Mar 2026, 4:40 p.m. | Last Modified: 11 Mar 2026, 4:40 p.m.

Panel Version: 8.25

Comment on list classification: As reviewed by Jenna Ridley, there are four unrelated cases/ families identified with four different heterozygous missense variants in FAT2 gene and reported with late-onset spinocerebellar ataxia. There is some functional work available.

This gene has been associated with relevant phenotype in OMIM (MIM #617769).

This gene should therefore be promoted to green rating in the next GMS update.

Created: 25 Apr 2025, 3:23 p.m. | Last Modified: 25 Apr 2025, 3:23 p.m.

Panel Version: 7.22

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Spinocerebellar ataxia 45, OMIM:617769

Publications

• 29053796
• 33884300
• 36339299

Green List (high evidence)

PMID: 29053796 reported a family (RF14) in which 6 patients spanning 2 generations had late-onset spinocerebellar ataxia after age 40. The proband was noted to have a relatively pure cerebellar syndrome with limb and gait ataxia, downbeat nystagmus, and dysarthria. No detailed clinical information was available for the remaining affected family members. Testing of 5 of the affected individuals was undertaken and c.10758G>C p.(Lys3586Asn) variant was identified in all. Two unaffected members were tested and did not harbour the variant.

An unrelated patient (case DNA056251) had onset of slowly progressive gait and limb ataxia and dysarthria at around 50 years of age. He did not have nystagmus. Brain MRI showed atrophy of the cerebellar vermis and hemosiderin deposits in the mesencephalon. This individual harboured c.10946G>A p.(Ar3649Glu)

PMID: 36339299 reported an 82yo male with a strong f/h of gait imbalance, horizontal gaze evoked nystagmus and ataxic dysarthria. A missense FAT2 variant p.(Met1705Thr) was identified. The variant also detected in his symptomatic surviving brother.

PMID: 33884300 reported 2 siblings with late onset cerebellar ataxia and mild cerebellar atrophy, both with a FAT2 p.(Tyr3636Asp) variant

Only missense variants have been reported.
Sources: Literature

Created: 21 Feb 2025, 1:20 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Spinocerebellar ataxia 45, OMIM:617769

Publications

• 29053796
• 36339299
• 33884300

Mode of pathogenicity
Other