Biallelic SQSTM1 mutations in early-onset, variably progressive neurodegeneration
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