Biallelic CHP1 mutation causes human autosomal recessive ataxia by impairing NHE1 function.

ABSTRACT:

Objective

To ascertain the genetic and functional basis of complex autosomal recessive cerebellar ataxia (ARCA) presented by 2 siblings of a consanguineous family characterized by motor neuropathy, cerebellar atrophy, spastic paraparesis, intellectual disability, and slow ocular saccades.

Methods

Combined whole-genome linkage analysis, whole-exome sequencing, and focused screening for identification of potential causative genes were performed. Assessment of the functional consequences of the mutation on protein function via subcellular fractionation, size-exclusion chromatography, and fluorescence microscopy were done. A zebrafish model, using Morpholinos, was generated to study the pathogenic effect of the mutation in vivo.

Results

We identified a biallelic 3-bp dele

SUBMITTER: Mendoza-Ferreira N 

PROVIDER: S-EPMC5775069 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature