PMID- 28815558 OWN - NLM STAT- MEDLINE DCOM- 20171023 LR - 20210816 IS - 1600-0412 (Electronic) IS - 0001-6349 (Linking) VI - 96 IP - 11 DP - 2017 Nov TI - Sequence variants in ESR1 and OXTR are associated with Mayer-Rokitansky-Kuster-Hauser syndrome. PG - 1338-1346 LID - 10.1111/aogs.13202 [doi] AB - INTRODUCTION: Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS) is characterized by congenital absence of the uterus and the upper two-thirds of the vagina in otherwise phenotypically normal females. It is found isolated or associated with renal, skeletal and other malformations. Despite ongoing research, the etiology is mainly unknown. For a long time, the hypothesis of deficient hormone receptors as the cause for MRKHS has existed, supported by previous findings of our group. The aim of the present study was to identify unknown genetic causes for MRKHS and to compare them with data banks including a review of the literature. MATERIAL AND METHODS: DNA sequence analysis of the oxytocin receptor (OXTR) and estrogen receptor-1 gene (ESR1) was performed in a group of 93 clinically well-defined patients with uterovaginal aplasia (68 with the isolated form and 25 with associated malformations). RESULTS: In total, we detected three OXTR variants in 18 MRKHS patients with one leading to a missense mutation, and six ESR1 variants in 21 MRKHS patients, two of these causing amino acid changes and therefore potentially disease. CONCLUSIONS: The identified variants on DNA level might impair receptor function through different molecular mechanisms. Mutations of ESR1 and OXTR are associated with MRKHS. Thus, we consider these genes potential candidates associated with the manifestation of MRKHS. CI - (c) 2017 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica. FAU - Brucker, Sara Yvonne AU - Brucker SY AD - Department of Women's Health, Center for Rare Female Genital Malformations, Women's University Hospital, Tubingen University Hospital, Tubingen, Germany. AD - Department of Women's Health, Research Center for Women's Health, University Tubingen, Tubingen, Germany. FAU - Frank, Liliane AU - Frank L AD - Department of Women's Health, Research Center for Women's Health, University Tubingen, Tubingen, Germany. FAU - Eisenbeis, Simone AU - Eisenbeis S AD - Department of Women's Health, Research Center for Women's Health, University Tubingen, Tubingen, Germany. FAU - Henes, Melanie AU - Henes M AD - Department of Women's Health, Center for Rare Female Genital Malformations, Women's University Hospital, Tubingen University Hospital, Tubingen, Germany. FAU - Wallwiener, Diethelm AU - Wallwiener D AD - Department of Women's Health, Center for Rare Female Genital Malformations, Women's University Hospital, Tubingen University Hospital, Tubingen, Germany. FAU - Riess, Olaf AU - Riess O AD - Institute of Medical Genetics and Applied Genomics, Tubingen University Hospital, Tubingen, Germany. FAU - van Eijck, Barbara AU - van Eijck B AD - Department of Women's Health, Research Center for Women's Health, University Tubingen, Tubingen, Germany. FAU - Scholler, Dorit AU - Scholler D AD - Department of Women's Health, Center for Rare Female Genital Malformations, Women's University Hospital, Tubingen University Hospital, Tubingen, Germany. FAU - Bonin, Michael AU - Bonin M AD - Institute of Medical Genetics and Applied Genomics, Tubingen University Hospital, Tubingen, Germany. FAU - Rall, Kristin Katharina AU - Rall KK AUID- ORCID: 0000-0003-4546-9438 AD - Department of Women's Health, Center for Rare Female Genital Malformations, Women's University Hospital, Tubingen University Hospital, Tubingen, Germany. LA - eng SI - GENBANK/NM_000916.3 PT - Journal Article DEP - 20170921 PL - United States TA - Acta Obstet Gynecol Scand JT - Acta obstetricia et gynecologica Scandinavica JID - 0370343 RN - 0 (ESR1 protein, human) RN - 0 (Estrogen Receptor alpha) RN - 0 (Receptors, Oxytocin) RN - Mullerian aplasia SB - IM MH - 46, XX Disorders of Sex Development/*genetics MH - Adolescent MH - Adult MH - Congenital Abnormalities/*genetics MH - Estrogen Receptor alpha/*genetics MH - Female MH - Genetic Variation MH - Humans MH - Middle Aged MH - Mullerian Ducts/*abnormalities MH - Mutation, Missense MH - Receptors, Oxytocin/*genetics MH - Sequence Analysis, DNA OTO - NOTNLM OT - DNA OT - Mayer-Rokitansky-Kuster-Hauser syndrome OT - estrogen receptor-1 OT - oxytocin receptor OT - single nucleotide variation EDAT- 2017/08/18 06:00 MHDA- 2017/10/24 06:00 CRDT- 2017/08/18 06:00 PHST- 2017/05/29 00:00 [received] PHST- 2017/08/02 00:00 [accepted] PHST- 2017/08/18 06:00 [pubmed] PHST- 2017/10/24 06:00 [medline] PHST- 2017/08/18 06:00 [entrez] AID - 10.1111/aogs.13202 [doi] PST - ppublish SO - Acta Obstet Gynecol Scand. 2017 Nov;96(11):1338-1346. doi: 10.1111/aogs.13202. Epub 2017 Sep 21.