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

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

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objective 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 WNT4, HNF1B, and LHX1. The goals of this study were to: 1) determine the prevalence of WNT4, HNF1B, and LHX1 point mutations, as well as new copy number variants (CNVs) in people with MRKH; and 2) identify and characterize MRKH cohorts. Design Laboratory- and community-based study. Setting Academic medical centers. Patient(s) A total of 147 MRKH probands and available family members. Interventions(s) DNA sequencing of WNT4, HNF1B, 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. Result(s) We report finding CNVs in 6/31 people (∼19%) with MRKH, but no point mutations or small indels in WNT4, HNF1B, 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. Conclusion(s) Although the prevalence of WNT4, HNF1B, 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.

Original languageEnglish (US)
Pages (from-to)145-151.e2
JournalFertility and sterility
Volume108
Issue number1
DOIs
StatePublished - Jul 2017

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Point Mutation
Mullerian aplasia
Genetic Association Studies
Pedigree
Microarray Analysis
DNA Sequence Analysis
Genes
Outcome Assessment (Health Care)

Keywords

  • MRKH
  • Müllerian aplasia
  • congenital absence of the uterus and vagina
  • gene mutation
  • reproductive genetics

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Williams, L. S., Demir Eksi, D., Shen, Y., Lossie, A. C., Chorich, L. P., Sullivan, M. E., ... Layman, L. C. (2017). Genetic analysis of Mayer-Rokitansky-Kuster-Hauser syndrome in a large cohort of families. Fertility and sterility, 108(1), 145-151.e2. https://doi.org/10.1016/j.fertnstert.2017.05.017

Genetic analysis of Mayer-Rokitansky-Kuster-Hauser syndrome in a large cohort of families. / Williams, Lacey S.; Demir Eksi, Durkadin; Shen, Yiping; Lossie, Amy C.; Chorich, Lynn P.; Sullivan, Megan E.; Phillips, John A.; Erman, Munire; Kim, Hyung Goo; Alper, Ozgul M.; Layman, Lawrence C.

In: Fertility and sterility, Vol. 108, No. 1, 07.2017, p. 145-151.e2.

Research output: Contribution to journalArticle

Williams, LS, Demir Eksi, D, Shen, Y, Lossie, AC, Chorich, LP, Sullivan, ME, Phillips, JA, Erman, M, Kim, HG, Alper, OM & Layman, LC 2017, 'Genetic analysis of Mayer-Rokitansky-Kuster-Hauser syndrome in a large cohort of families', Fertility and sterility, vol. 108, no. 1, pp. 145-151.e2. https://doi.org/10.1016/j.fertnstert.2017.05.017
Williams LS, Demir Eksi D, Shen Y, Lossie AC, Chorich LP, Sullivan ME et al. Genetic analysis of Mayer-Rokitansky-Kuster-Hauser syndrome in a large cohort of families. Fertility and sterility. 2017 Jul;108(1):145-151.e2. https://doi.org/10.1016/j.fertnstert.2017.05.017
Williams, Lacey S. ; Demir Eksi, Durkadin ; Shen, Yiping ; Lossie, Amy C. ; Chorich, Lynn P. ; Sullivan, Megan E. ; Phillips, John A. ; Erman, Munire ; Kim, Hyung Goo ; Alper, Ozgul M. ; Layman, Lawrence C. / Genetic analysis of Mayer-Rokitansky-Kuster-Hauser syndrome in a large cohort of families. In: Fertility and sterility. 2017 ; Vol. 108, No. 1. pp. 145-151.e2.
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abstract = "Objective 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 WNT4, HNF1B, and LHX1. The goals of this study were to: 1) determine the prevalence of WNT4, HNF1B, and LHX1 point mutations, as well as new copy number variants (CNVs) in people with MRKH; and 2) identify and characterize MRKH cohorts. Design Laboratory- and community-based study. Setting Academic medical centers. Patient(s) A total of 147 MRKH probands and available family members. Interventions(s) DNA sequencing of WNT4, HNF1B, 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. Result(s) We report finding CNVs in 6/31 people (∼19{\%}) with MRKH, but no point mutations or small indels in WNT4, HNF1B, 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. Conclusion(s) Although the prevalence of WNT4, HNF1B, 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.",
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AU - Shen, Yiping

AU - Lossie, Amy C.

AU - Chorich, Lynn P.

AU - Sullivan, Megan E.

AU - Phillips, John A.

AU - Erman, Munire

AU - Kim, Hyung Goo

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