Genetic analysis of Mayer-Rokitansky-Kuster-Hauser syndrome in a large cohort of families

No WNT4, HNF1B, or LHX1 point mutations were found in people with Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH), but w19% had copy number variants. We characterized and collected samples from 147 MRKH families, which will facilitate future genetic analyses.

Like Comment

Volume 108, Issue 1, Pages 145–151.e2


Lacey S. Williams, B.S., Durkadin Demir Eksi, Ph.D., Yiping Shen, Ph.D., Amy C. Lossie, Ph.D., Lynn P. Chorich, M.S., Megan E. Sullivan, B.S., John A. Phillips III, M.D., Munire Erman, M.D., Hyung-Goo Kim, Ph.D., Ozgul M. Alper, Ph.D., Lawrence C. Layman, M.D.



To study the genetic cause of Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH). Although a few candidate genes and genomic domains for have been reported for MRKH, the genetic underpinnings remain largely unknown. Some of the top candidate genes are WNT4HNF1B, and LHX1. The goals of this study were to: 1) determine the prevalence of WNT4HNF1B, and LHX1 point mutations, as well as new copy number variants (CNVs) in people with MRKH; and 2) identify and characterize MRKH cohorts.


Laboratory- and community-based study.


Academic medical centers.


A total of 147 MRKH probands and available family members.


DNA sequencing of WNT4HNF1B, and LHX1 in 100 MRKH patients, chromosomal microarray analysis in 31 North American MRKH patients, and characterization and sample collection of 147 North American and Turkish MRKH probands and their families.

Main Outcome Measure(s)

DNA sequence variants and CNVs; pedigree structural analysis.


We report finding CNVs in 6/31 people (∼19%) with MRKH, but no point mutations or small indels in WNT4HNF1B, or LHX1 in 100 MRKH patients. Our MRKH families included 43 quads, 26 trios, and 30 duos. Of our MRKH probands, 87/147 (59%) had MRKH type 1 and 60/147 (41%) had type 2 with additional anomalies.


Although the prevalence of WNT4HNF1B, and LHX1 point mutations is low in people with MRKH, the prevalence of CNVs was ∼19%. Further analysis of our large familial cohort of patients will facilitate gene discovery to better understand the complex etiology of MRKH.

Read the full text here.

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.