Biallelic mutation of HSD17B4 induces middle age-onset spinocerebellar ataxia.

ABSTRACT:

Objective

To determine the genetic underpinnings of slowly progressive spinocerebellar ataxia, autosomal recessive (SCAR), we performed exome analysis and examined the relationship between clinical severity and functional change induced by the mutation.

Methods

Homozygosity fingerprinting and exome sequencing were performed to identify causative mutations in 2 consanguineous families. We assessed the expression of D-bifunctional protein (DBP) and the amount of dimerized DBP in fibroblasts by immunoblot and quantitative reverse transcription PCR. The pathogenicity of the mutation was evaluated using the Combined Annotation-Dependent Depletion (CADD) scores; these results were compared with the scores of previously reported mutations.

Results

We identified a homozygous

SUBMITTER: Matsuda Y 

PROVIDER: S-EPMC6975179 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature