Inherited SHQ1 mutations impair interaction with NAP57/dyskerin, a major target in dyskeratosis congenita.

ABSTRACT:

Background

The inherited bone marrow failure syndrome dyskeratosis congenita (DC) is most frequently caused by mutations in DKC1 (MIM# 300126), the gene encoding NAP57 (aka dyskerin). The typically missense mutations modulate the interaction of NAP57 with its chaperone SHQ1, but no DC mutations have been identified in SHQ1 (MIM# 613663). Here, we report on two compound heterozygous mutations in SHQ1 in a patient with a severe neurological disorder including cerebellar degeneration.

Methods

The SHQ1 mutations were identified by patient exome sequencing. The impact of the mutations was assessed in pulldown assays with recombinant NAP57.

Results

The SHQ1 mutations were the only set of mutations consistent with an autosomal recessive mode of inheritance. The mutations map

SUBMITTER: Bizarro J 

PROVIDER: S-EPMC5702568 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature