Mutations in Twinkle primase-helicase cause Perrault syndrome with neurologic features.

ABSTRACT:

Objective

To identify the genetic cause in 2 families of progressive ataxia, axonal neuropathy, hyporeflexia, and abnormal eye movements, accompanied by progressive hearing loss and ovarian dysgenesis, with a clinical diagnosis of Perrault syndrome.

Methods

Whole-exome sequencing was performed to identify causative mutations in the 2 affected sisters in each family. Family 1 is of Japanese ancestry, and family 2 is of European ancestry.

Results

In family 1, affected individuals were compound heterozygous for chromosome 10 open reading frame 2 (C10orf2) p.Arg391His and p.Asn585Ser. In family 2, affected individuals were compound heterozygous for C10orf2 p.Trp441Gly and p.Val507Ile. C10orf2 encodes Twinkle, a primase-helicase essential for replication of mitochondrial D

SUBMITTER: Morino H 

PROVIDER: S-EPMC4248451 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature