A novel hypomorphic splice variant in EIF2B5 gene is associated with mild ovarioleukodystrophy.

ABSTRACT:

Objective

To identify the genetic cause in an adult ovarioleukodystrophy patient resistant to diagnosis.

Methods

We applied whole-exome sequencing (WES) to a vanishing white matter disease patient associated with premature ovarian failure at 26 years of age. We functionally tested an intronic variant by RT-PCR on patient's peripheral blood mononuclear cells (PBMC) and by minigene splicing assay.

Results

WES analysis identified two novel variants in the EIF2B5 gene: c.725A > G (p.Tyr242Cys) and an intronic noncanonical mutation (c.1156 + 13G>A). This intronic mutation resulted into generation of various isoforms both in patient's PBMC and in the minigene splicing assay, showing that ~20% residual wild-type isoform is still expressed by the intronic-mutated allele alone

SUBMITTER: Rodriguez-Palmero A 

PROVIDER: S-EPMC7480926 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature