A Study of Splicing Mutations in Disorders of Sex Development

Overview

Journal Sci Rep

Specialty Science

Date 2017 Nov 28

PMID 29176693

Citations 3

Authors

Flavia Leme de Calais

Lindsay D Smith

Michela Raponi

Andrea Trevas Maciel-Guerra

Gil Guerra-Junior

Maricilda Palandi de Mello

Diana Baralle

Affiliations

Soon will be listed here.

Abstract

The presence of splicing sequence variants in genes responsible for sex development in humans may compromise correct biosynthesis of proteins involved in the normal development of gonads and external genitalia. In a cohort of Brazilian patients, we identified mutations in HSD17B3 and SRD5A2 which are both required for human sexual differentiation. A number of these mutations occurred within regions potentially critical for splicing regulation. Minigenes were used to validate the functional effect of mutations in both genes. We evaluated the c.277 + 2 T > G mutation in HSD17B3, and the c.544 G > A, c.548-44 T > G and c.278delG mutations in SRD5A2. We demonstrated that these mutations altered the splicing pattern of these genes. In a genomic era these results illustrate, and remind us, that sequence variants within exon-intron boundaries, which are primarily identified for diagnostic purposes and have unknown pathogenicity, need to be assessed with regards to their impact not only on protein expression, but also on mRNA splicing.

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