Homozygous pathogenic variant in BRAT1 associated with nonprogressive cerebellar ataxia.

ABSTRACT:

Objective

To investigate the pathogenicity of a novel homozygous BRAT1 variant in 2 siblings with nonprogressive cerebellar ataxia (NPCA) through functional studies on primary and immortalized patient cell lines.

Methods

BRAT1 protein levels and ataxia-telangiectasia mutated (ATM) kinase activity in patient-derived and control cell lines were assessed by Western blotting. The impact of the novel BRAT1 variants on mitochondrial function was also assessed, by comparing patient and control cell lines for rates of oxygen consumption and for phosphorylation (S293) of the E1⍺ subunit of pyruvate dehydrogenase (PDH).

Results

Two male siblings with NPCA, mild intellectual disability, and isolated cerebellar atrophy were found to be homozygous for a c.185T>A (p.V

SUBMITTER: Mahjoub A 

PROVIDER: S-EPMC6773431 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature