Mutation in POLR3K causes hypomyelinating leukodystrophy and abnormal ribosomal RNA regulation.

ABSTRACT:

Objective

To identify the genetic cause of hypomyelinating leukodystrophy in 2 consanguineous families.

Methods

Homozygosity mapping combined with whole-exome sequencing of consanguineous families was performed. Mutation consequences were determined by studying the structural change of the protein and by the RNA analysis of patients' fibroblasts.

Results

We identified a biallelic mutation in a gene coding for a Pol III-specific subunit, POLR3K (c.121C>T/p.Arg41Trp), that cosegregates with the disease in 2 unrelated patients. Patients expressed neurologic and extraneurologic signs found in POLR3A- and POLR3B-related leukodystrophies with a peculiar severe digestive dysfunction. The mutation impaired the POLR3K-POLR3B interactions resulting in zebra

SUBMITTER: Dorboz I 

PROVIDER: S-EPMC6283457 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature