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Original Article
Sex Dev 2019;13:26–34
DOI: 10.1159/000494896
Identification of Candidate Genes
for Mayer-Rokitansky-Küster-Hauser
Syndrome Using Genomic Approaches
Brendan Backhouse
a
Chloe Hanna
b, c
Gorjana Robevska
a
Jocelyn van den Bergen
a
Emanuele Pelosi
e
Cas Simons
b
Peter Koopman
e
A. Zulfa Juniarto
f
Sonia Grover
a–c
Sultana Faradz
f
Andrew Sinclair
a, b, d
Katie Ayers
a, b
Tiong Y. Tan
a–d
a
Department of Paediatrics, University of Melbourne,
b
Murdoch Children’s Research Institute,
c
Royal Children’s
Hospital,
d
Victorian Clinical Genetics Services, Melbourne, VIC, and
e
Institute for Molecular Bioscience,
The University of Queensland, Brisbane, QLD, Australia;
f
Center for Biomedical Research, Faculty of Medicine,
Diponegoro University (FMDU), Semarang, Indonesia
contributing variants. Microarray analysis identified a 0.6-Mb
deletion in the previously implicated 16p11.2 region in a pa-
tient with MRKH type 2. WES revealed 16 rare nonsynony-
mous 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 delin-
eate their biological significance and expand the genotypic
spectrum of MRKH. © 2018 S. Karger AG, Basel
Mayer-Rokitansky-Küster-Hauser (MRKH) syn-
drome (OMIM 277000) is a congenital disorder of sex
development (DSD). It affects the female reproductive
tract of approximately 1 in 4,500 females and is charac-
Keywords
Genotype · MURCS · Phenotype · Whole exome sequencing
Abstract
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a dis-
order of sex development which affects 1 in 4,500 females
and is characterized by agenesis of müllerian structures, in-
cluding 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 be-
coming 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 unre-
lated women with MRKH and MURCS. WES data were ana-
lysed using a candidate gene approach to identify potential
Accepted: July 18, 2018
Published online: December 1, 2018
Tiong Yang Tan
Murdoch Children’s Research Institute
Royal Children’s Hospital
Flemington Road, Parkville, Melbourne, VIC 3052 (Australia)
E-Mail tiong.tan @ vcgs.org.au
© 2018 S. Karger AG, Basel
www.karger.com/sxd
K.A. and T.Y.T contributed equally to this work.