Open AccessIdentification of Candidate Genes for Mayer-Rokitansky-Küster-Hauser Syndrome Using Genomic Approaches
Author(s) -
Brendan Backhouse,
Chloe Hanna,
Gorjana Robevska,
Jocelyn van den Bergen,
Emanuele Pelosi,
Cas Simons,
Peter Koopman,
Achmad Zulfa Juniarto,
Sonia Grover,
Sultana Mh Faradz,
Andrew H. Sinclair,
Katie Ayers,
Tiong Yang Tan
Publication year - 2018
Publication title -
sexual development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 44
eISSN - 1661-5433
pISSN - 1661-5425
DOI - 10.1159/000494896
Subject(s) - biology , candidate gene , exome sequencing , genetics , mayer rokitansky kuster hauser syndrome , nonsynonymous substitution , gene , mullerian ducts , vagina , uterus , mutation , genome
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder of sex development which affects 1 in 4,500 females and is characterized by agenesis of müllerian structures, including the uterus, cervix, and upper vagina. It can occur in isolation (type 1) or in conjunction with various anomalies (type 2), with a subset of these comprising müllerian, renal, and cervicothoracic abnormalities (MURCS) association. The genetic causes of MRKH have been investigated previously yielding limited results, with massive parallel sequencing becoming increasingly utilized. We sought to identify genetic contributions to MRKH using a combination of microarray and whole exome sequencing (WES) on a cohort of 8 unrelated women with MRKH and MURCS. WES data were analysed using a candidate gene approach to identify potential contributing variants. Microarray analysis identified a 0.6-Mb deletion in the previously implicated 16p11.2 region in a patient with MRKH type 2. WES revealed 16 rare nonsynonymous variants in MRKH candidate genes across the cohort. These included variants in several genes, such as LRP10 and DOCK4, associated with disorders with müllerian anomalies. Further functional studies of these variants will help to delineate their biological significance and expand the genotypic spectrum of MRKH.