Biallelic SQSTM1 mutations in early-onset, variably progressive neurodegeneration.

ABSTRACT:

Objective

To characterize clinically and molecularly an early-onset, variably progressive neurodegenerative disorder characterized by a cerebellar syndrome with severe ataxia, gaze palsy, dyskinesia, dystonia, and cognitive decline affecting 11 individuals from 3 consanguineous families.

Methods

We used whole-exome sequencing (WES) (families 1 and 2) and a combined approach based on homozygosity mapping and WES (family 3). We performed in vitro studies to explore the effect of the nontruncating SQSTM1 mutation on protein function and the effect of impaired SQSTM1 function on autophagy. We analyzed the consequences of sqstm1 down-modulation on the structural integrity of the cerebellum in vivo using zebrafish as a model.

Results

We identified 3 homozygous inacti

SUBMITTER: Muto V 

PROVIDER: S-EPMC6070386 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature