DOCSLIB.ORG

Thesis Hsf 2018 Maison Patrick

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Thesis Hsf 2018 Maison Patrick Genetic Basis of Human Disorders of Gonadal Development PATRICK OPOKU MANU MAISON University of Cape Town A dissertation submitted in fulfillment of the requirements for the degree of Master of Science in Urology in the Faculty of Health Sciences, at the University of the Cape Town Cape Town, South Africa, 2017. i The copyright of this thesis vests in the author. No quotation from it or information derived from it is to be published without full acknowledgement of the source. The thesis is to be used for private study or non- commercial research purposes only. Published by the University of Cape Town (UCT) in terms of the non-exclusive license granted to UCT by the author. University of Cape Town Contents LIST OF TABLES .............................................................................................................................................. v LIST OF FIGURES ........................................................................................................................................... vi LIST OF ABBREVIATIONS ............................................................................................................................. vii DECLARATION: ........................................................................................................................................ ix ABSTRACT .................................................................................................................................................. x ACKNOWLEDGEMENT ..........................................................................................................................xiii CHAPTER ONE ........................................................................................................................................... 1 1.1 Rationale for the Study ........................................................................................................................... 1 CHAPTER TWO .......................................................................................................................................... 4 2.0. INTRODUCTION ................................................................................................................................. 4 2.1. Disorder of Sexual Differentiation ......................................................................................................... 4 2.1.1 Ovotesticular DSD ............................................................................................................................... 5 2.1.2. Classification of Ovotesticular DSDs ................................................................................................. 5 2.1.3. Clinical features of Ovotesticular DSD .............................................................................................. 6 2.1.3.2. The types of gonads ......................................................................................................................... 7 2.1.3.3 The distribution of gonads ................................................................................................................ 7 2.1.3.4 Distribution of karyotype .................................................................................................................. 9 2.1.3.5 External genitalia ............................................................................................................................ 10 2.1.4 Diagnosis............................................................................................................................................ 10 2.1.5 Sex of rearing ..................................................................................................................................... 11 2.1.6Management ........................................................................................................................................ 11 2.1.6.1 Surgical treatment ........................................................................................................................... 11 2.1.6.2 Sex Steroid Replacement .............................................................................................................. 12 2.1.6.3 Psychosocial management .............................................................................................................. 13 2.1.7 Prevalence of 46XX Ovotesticular DSD in South Africa .................................................................. 13 2.1.7.2. Familial incidence .......................................................................................................................... 14 2.2. The aetiology of 46XX Ovotesticular DSD ......................................................................................... 14 2.2.1. Normal fetal sex determination and gonadal differentiation ............................................................. 15 2.2.2. Chromosomal, gonadal and phenotypic sex ..................................................................................... 15 2.2.2. Gonadal differentiation and growth in Ovotesticular DSD ............................................................... 16 2.2.3 Mechanisms Underlying Testis Differentiation in SRY -Negative Individuals .................................. 17 ii SOX3 .......................................................................................................................................................... 18 DMRT1 ....................................................................................................................................................... 19 2.2.3.2 Insufficient Expression of Pro-Ovarian Genes ............................................................................... 19 WNT4 ......................................................................................................................................................... 19 RSPO1 ........................................................................................................................................................ 20 FOXL2 ........................................................................................................................................................ 20 2.3. Models for mammalian sex determination ........................................................................................... 21 2.3.1. The SOX model ................................................................................................................................ 21 2.3.2. The Z gene model ............................................................................................................................. 21 2.3.3. The DSS-gene model ........................................................................................................................ 22 2.3. 4 A proposed cascade for sex determination ....................................................................................... 22 2.4 A hypothesis on the molecular aetiology of Ovotesticular DSD ......................................................... 23 3.0 Materials and Methods .......................................................................................................................... 25 3.1 Study Site .............................................................................................................................................. 25 3.2 Study Participants ................................................................................................................................. 25 3.2. 1 Inclusion Criteria .............................................................................................................................. 25 3.2.2 Exclusion Criteria ............................................................................................................................ 25 3.3 Study Design ......................................................................................................................................... 25 3.4Sample/ Data Management: ................................................................................................................... 26 3.4.1 Massively parallel sequencing. .......................................................................................................... 26 3.4.2 Functional effects of mutations. ......................................................................................................... 27 3.5 Data Analysis ........................................................................................................................................ 30 3.6 Ethical and legal considerations ............................................................................................................ 35 CHAPTER FOUR ....................................................................................................................................... 36 4.0 RESULTS ............................................................................................................................................. 36 Clinical Findings ......................................................................................................................................... 36 Histologic Findings ..................................................................................................................................... 36 Gonadal Laterality and Distribution ........................................................................................................... 36 Laparoscopic Findings ...............................................................................................................................
Load more

Recommended publications
  • Müllerian Aplasia and Hyperandrogenism
    Müllerian aplasia and hyperandrogenism Description Müllerian aplasia and hyperandrogenism is a condition that affects the reproductive system in females. This condition is caused by abnormal development of the Müllerian ducts, which are structures in the embryo that develop into the uterus, fallopian tubes, cervix, and the upper part of the vagina. Individuals with Müllerian aplasia and hyperandrogenism typically have an underdeveloped or absent uterus and may also have abnormalities of other reproductive organs. Women with this condition have normal female external genitalia, and they develop breasts and pubic hair normally at puberty; however, they do not begin menstruation by age 16 (primary amenorrhea) and will likely never have a menstrual period. Affected women are unable to have children ( infertile). Women with Müllerian aplasia and hyperandrogenism have higher-than-normal levels of male sex hormones called androgens in their blood (hyperandrogenism), which can cause acne and excessive facial hair (facial hirsutism). Kidney abnormalities may be present in some affected individuals. Frequency Müllerian aplasia and hyperandrogenism is a very rare disorder; it has been identified in only a few individuals worldwide. Causes Mutations in the WNT4 gene cause Müllerian aplasia and hyperandrogenism. This gene belongs to a family of WNT genes that play critical roles in development before birth. The WNT4 gene provides instructions for producing a protein that is important for the formation of the female reproductive system, the kidneys, and several hormone- producing glands. During the development of the female reproductive system, the WNT4 protein regulates the formation of the Müllerian ducts. This protein is also involved in development of the ovaries, from before birth through adulthood, and is important for development and maintenance of egg cells (oocytes) in the ovaries.
    [Show full text]
  • Orphanet Report Series Rare Diseases Collection
    Marche des Maladies Rares – Alliance Maladies Rares Orphanet Report Series Rare Diseases collection DecemberOctober 2013 2009 List of rare diseases and synonyms Listed in alphabetical order www.orpha.net 20102206 Rare diseases listed in alphabetical order ORPHA ORPHA ORPHA Disease name Disease name Disease name Number Number Number 289157 1-alpha-hydroxylase deficiency 309127 3-hydroxyacyl-CoA dehydrogenase 228384 5q14.3 microdeletion syndrome deficiency 293948 1p21.3 microdeletion syndrome 314655 5q31.3 microdeletion syndrome 939 3-hydroxyisobutyric aciduria 1606 1p36 deletion syndrome 228415 5q35 microduplication syndrome 2616 3M syndrome 250989 1q21.1 microdeletion syndrome 96125 6p subtelomeric deletion syndrome 2616 3-M syndrome 250994 1q21.1 microduplication syndrome 251046 6p22 microdeletion syndrome 293843 3MC syndrome 250999 1q41q42 microdeletion syndrome 96125 6p25 microdeletion syndrome 6 3-methylcrotonylglycinuria 250999 1q41-q42 microdeletion syndrome 99135 6-phosphogluconate dehydrogenase 67046 3-methylglutaconic aciduria type 1 deficiency 238769 1q44 microdeletion syndrome 111 3-methylglutaconic aciduria type 2 13 6-pyruvoyl-tetrahydropterin synthase 976 2,8 dihydroxyadenine urolithiasis deficiency 67047 3-methylglutaconic aciduria type 3 869 2A syndrome 75857 6q terminal deletion 67048 3-methylglutaconic aciduria type 4 79154 2-aminoadipic 2-oxoadipic aciduria 171829 6q16 deletion syndrome 66634 3-methylglutaconic aciduria type 5 19 2-hydroxyglutaric acidemia 251056 6q25 microdeletion syndrome 352328 3-methylglutaconic
    [Show full text]
  • Genetics, Underlying Pathologies and Psychosexual Differentiation Valerie A
    REVIEWS DSDs: genetics, underlying pathologies and psychosexual differentiation Valerie A. Arboleda, David E. Sandberg and Eric Vilain Abstract | Mammalian sex determination is the unique process whereby a single organ, the bipotential gonad, undergoes a developmental switch that promotes its differentiation into either a testis or an ovary. Disruptions of this complex genetic process during human development can manifest as disorders of sex development (DSDs). Sex development can be divided into two distinct processes: sex determination, in which the bipotential gonads form either testes or ovaries, and sex differentiation, in which the fully formed testes or ovaries secrete local and hormonal factors to drive differentiation of internal and external genitals, as well as extragonadal tissues such as the brain. DSDs can arise from a number of genetic lesions, which manifest as a spectrum of gonadal (gonadal dysgenesis to ovotestis) and genital (mild hypospadias or clitoromegaly to ambiguous genitalia) phenotypes. The physical attributes and medical implications associated with DSDs confront families of affected newborns with decisions, such as gender of rearing or genital surgery, and additional concerns, such as uncertainty over the child’s psychosexual development and personal wishes later in life. In this Review, we discuss the underlying genetics of human sex determination and focus on emerging data, genetic classification of DSDs and other considerations that surround gender development and identity in individuals with DSDs. Arboleda, V. A. et al. Nat. Rev. Endocrinol. advance online publication 5 August 2014; doi:10.1038/nrendo.2014.130 Introduction Sex development is a critical component of mammalian disrupted, which occurs primarily as a result of genetic development that provides a robust mechanism for con- mutations that interfere with either the development of tinued generation of genetic diversity within a species.
    [Show full text]
  • Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome a Comprehensive Update Herlin, Morten Krogh; Petersen, Michael Bjørn; Brännström, Mats
    Aalborg Universitet Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome a comprehensive update Herlin, Morten Krogh; Petersen, Michael Bjørn; Brännström, Mats Published in: Orphanet Journal of Rare Diseases DOI (link to publication from Publisher): 10.1186/s13023-020-01491-9 Creative Commons License CC BY 4.0 Publication date: 2020 Document Version Publisher's PDF, also known as Version of record Link to publication from Aalborg University Citation for published version (APA): Herlin, M. K., Petersen, M. B., & Brännström, M. (2020). Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: a comprehensive update. Orphanet Journal of Rare Diseases, 15(1), [214]. https://doi.org/10.1186/s13023-020- 01491-9 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. ? Users may download and print one copy of any publication from the public portal for the purpose of private study or research. ? You may not further distribute the material or use it for any profit-making activity or commercial gain ? You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us at [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from vbn.aau.dk on: September 27,
    [Show full text]
  • Cell-Intrinsic Wnt4 Controls Early Cdc1 Commitment and Suppresses
    bioRxiv preprint doi: https://doi.org/10.1101/469155; this version posted November 14, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Cell-intrinsic Wnt4 controls early cDC1 commitment and suppresses development of pathogen-specific Type 2 immunity Li-Yin Hung, Yingbiao Ji, David A. Christian, *Karl R. Herbine, *Christopher F. Pastore and De’Broski R. Herbert Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania *These authors contributed equally Corresponding Author: De’Broski R. Herbert, Ph.D. School of Veterinary Medicine, University of Pennsylvania Philadelphia, PA, 19104 Tel: (215) 898-9151 Fax (215) 206-8091 [email protected] bioRxiv preprint doi: https://doi.org/10.1101/469155; this version posted November 14, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Whether conventional dendritic cell (cDC) precursors acquire lineage-specific identity under direction of regenerative secreted glycoproteins within bone marrow niches is entirely unknown. Herein, we demonstrate that Wnt4, a beta-catenin independent Wnt ligand, is both necessary and sufficient for necessary for the full extent of pre-cDC1 specification within bone marrow. Cell-intrinsic Wnt4 deficiency in CD11c+ cells reduced mature cDC1 numbers in BM, spleen, lung, and intestine and, reciprocally, rWnt4 treatment promoted pJNK activation and cDC1 expansion. Lack of cell-intrinsic Wnt4 in mice CD11cCreWnt4flox/flox impaired stabilization of IRF8/cJun complexes in BM and increased the basal frequency of both cDC2 and ILC2 populations in the periphery.
    [Show full text]
  • Université De POITIERS Faculté De Médecine Et De Pharmacie THESE
    Université de POITIERS Faculté de Médecine et de Pharmacie Année 2015 thèse n° THESE Pour le diplôme d’état de docteur en médecine (Décret n°2004-67 du 16 janvier 2004) Présentée et soutenue publiquement le 05 février 2015, à Poitiers par Monsieur ANDRIEU Alban Né le 02/03/1979 Syndrome de Mayer Rokitansky Küster Hauser Mise à jour des thérapeutiques et vécu de trois patientes au CH de Saintes Composition du Jury Président : - Monsieur le Professeur José Gomes Da Cunha Membres : - Monsieur le Professeur Jean pierre Richer - Monsieur le Professeur Ludovic Gicquel - Monsieur le Docteur Bernard Freche Directeur de Thèse : Monsieur le Docteur Cambon ! ,! ! -! Université de POITIERS Faculté de Médecine et de Pharmacie Année 2015 thèse n° THESE Pour le diplôme d’état de docteur en médecine (décret n°2004-67 du 16 janvier 2004) Présentée et soutenue publiquement le 05 février 2015, à Poitiers par Monsieur ANDRIEU Alban Né le 02/03/1979 Syndrome de Mayer Rokitansky Küster Hauser Mise à jour des thérapeutiques et vécu de trois patientes au CH de Saintes Composition du Jury Président : Monsieur le Professeur José Gomes Da Cunha Membres : - Monsieur le Professeur Jean pierre Richer - Monsieur le Professeur Ludovic Gicquel - Monsieur le Docteur Bernard Freche Directeur de Thèse : Monsieur le Docteur Cambon ! .! ("#) %'#( )* )$,#(# %') !"#-(,.()*( .)*#,-*(%,()*(./"01"#,%( Année universitaire 2014 - 2015 LISTE DES ENSEIGNANTS DE MEDECINE Professeurs des Universités-Praticiens Hospitaliers 1. AGIUS Gérard, bactériologie-virologie 55. PERAULT Marie-Christine, pharmacologie clinique 2. ALLAL Joseph, thérapeutique 56. PERDRISOT Rémy, biophysique et médecine nucléaire 3. BATAILLE Benoît, neurochirurgie 57. PIERRE Fabrice, gynécologie et obstétrique 4. BENSADOUN René-Jean, cancérologie – radiothérapie (en 58.
    [Show full text]
  • From Gene to Gender - What We’Ve Learned and What We Need to Learn - New Prospects in DSD Research
    3rd International Symposium on Disorders of Sex Development 20 – 22 May 2011 · Universität zu Lübeck Programme & Abstracts From Gene to Gender - What we’ve learned and what we need to learn - New Prospects in DSD Research Sessions on Genetics, Hormones & Action, Morphologic Variation in DSD and Clinical Aspects · Round Table · Poster Session and Oral Sessions 20 – 22 May 2011, Lübeck, Germany 1 Contents Contents...................................................................................................................................1 Welcome Remarks ...................................................................................................................3 About EuroDSD........................................................................................................................4 General Information..................................................................................................................5 Scientific Programme ...............................................................................................................6 Social Programme....................................................................................................................9 Speakers’ List.........................................................................................................................10 Poster Presentation................................................................................................................12 Abstracts Keynote Lectures ...................................................................................................15
    [Show full text]
  • Universidade De Brasília Instituto De Ciências Biológicas Programa De Pós Graduação Em Biologia Animal
    UNIVERSIDADE DE BRASÍLIA INSTITUTO DE CIÊNCIAS BIOLÓGICAS PROGRAMA DE PÓS GRADUAÇÃO EM BIOLOGIA ANIMAL GABRIELA CORASSA RODRIGUES DA CUNHA AVALIAÇÃO GENÉTICA EM MULHERES DIAGNOSTICADAS CLINICAMENTE COM SÍNDROME DE MAYER-ROKITANSKY-KÜSTER-HAUSER Orientadora: Professora Doutora Aline Pic-Taylor BRASÍLIA 2018 UNIVERSIDADE DE BRASÍLIA INSTITUTO DE CIÊNCIAS BIOLÓGICAS DEPARTAMENTO DE BIOLOGIA ANIMAL PROGRAMA DE PÓS GRADUAÇÃO EM BIOLOGIA ANIMAL GABRIELA CORASSA RODRIGUES DA CUNHA AVALIAÇÃO GENÉTICA EM MULHERES DIAGNOSTICADAS CLINICAMENTE COM SÍNDROME DE MAYER-ROKITANSKY-KÜSTER-HAUSER Dissertação apresentada como requisito parcial para a obtenção do Título de Mestre em Biologia Animal, pelo Programa de Pós-Graduação em Biologia Animal, da Universidade de Brasília (UnB). Orientadora: Dra. Aline Pic-Taylor BRASÍLIA 2018 Dedico este trabalho aos meus pais, Lucas Rodrigues e Fernanda Corassa, por toda a importância que têm em minha vida, por todo apoio e pelas palavras de carinho e conforto. Sem vocês esse trabalho não teria sido possível. AGRADECIMENTOS Primeiramente, gostaria de agradecer a Deus pelas maravilhas que faz em minha vida. Agradeço também à minha orientadora, Drª Aline Pic Taylor, por ter me aceitado como orientanda e por ter confiado em mim durante todo o percurso desse mestrado. À Drª Juliana Mazzeu pela disponibilidade e pelos ensinamentos em genética clínica e molecular. Agradeço à equipe de médicos do Ambulatório de Genética Médica, por todo o suporte oferecido para a realização desse trabalho. Ao Dr Marcus Von Zuben pela avaliação das pacientes no âmbito da ginecologia e pela paciência em sanar minhas dúvidas. À equipe de endocrinologia, em especial à Drª Adriana Lofrano, por ser sempre tão generosa e prestativa para discussão dos casos avaliados.
    [Show full text]
  • Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome
    Orphanet Journal of Rare Diseases BioMed Central Review Open Access Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome Karine Morcel1,2, Laure Camborieux3, Programme de Recherches sur les Aplasies Müllériennes (PRAM)4 and Daniel Guerrier*1 Address: 1CNRS UMR 6061, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1, IFR140 GFAS, Faculté de Médecine, Rennes, France, 2Département d'Obstétrique, Gynécologie et Médecine de la Reproduction Hôpital Anne de Bretagne, Rennes, France, 3Association MAIA, Toulouse, France and 4Programme de Recherches sur les Aplasies Müllériennes (PRAM) – Coordination at: CNRS UMR 6061, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1, IFR140 GFAS, Faculté de Médecine, Rennes, France Email: Karine Morcel - [email protected]; Laure Camborieux - [email protected]; Programme de Recherches sur les Aplasies Müllériennes (PRAM) - [email protected]; Daniel Guerrier* - [email protected] * Corresponding author Published: 14 March 2007 Received: 16 October 2006 Accepted: 14 March 2007 Orphanet Journal of Rare Diseases 2007, 2:13 doi:10.1186/1750-1172-2-13 This article is available from: http://www.OJRD.com/content/2/1/13 © 2007 Morcel et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part (2/3) of the vagina in women showing normal development of secondary sexual characteristics and a normal 46, XX karyotype.
    [Show full text]
  • 'Control of Sex Development'
    Biason-Lauber, A (2010). Control of sex development. Best Practice and Research Clinical Endocrinology & Metabolism, 24(2):163-86. Postprint available at: http://www.zora.uzh.ch University of Zurich Posted at the Zurich Open Repository and Archive, University of Zurich. Zurich Open Repository and Archive http://www.zora.uzh.ch Originally published at: Best Practice and Research Clinical Endocrinology & Metabolism 2010, 24(2):163-86. Winterthurerstr. 190 CH-8057 Zurich http://www.zora.uzh.ch Year: 2010 Control of sex development Biason-Lauber, A Biason-Lauber, A (2010). Control of sex development. Best Practice and Research Clinical Endocrinology & Metabolism, 24(2):163-86. Postprint available at: http://www.zora.uzh.ch Posted at the Zurich Open Repository and Archive, University of Zurich. http://www.zora.uzh.ch Originally published at: Best Practice and Research Clinical Endocrinology & Metabolism 2010, 24(2):163-86. CONTROL OF SEX DEVELOPMENT Anna Biason-Lauber University Children’s Hospital, Zurich, Switzerland Correspondence to : Anna Biason-Lauber, MD University Children’s Hospital Div. of Endocrinology/Diabetology Steinwiesstrasse 75 CH-8032 Zurich Switzerland Tel + 41 44 266 7623 Fax + 41 44 266 7169 E-mail: [email protected] 1 ABSTRACT The process of sexual differentiation is central for reproduction of almost all metazoan, and therefore for maintenance of practically all multicellular organisms. In sex development we can distinguish two different processes¸ sex determination , that is the developmental decision that directs the undifferentiated embryo into a sexually dimorphic individual. In mammals, sex determination equals gonadal development. The second process known as sex differentiation takes place once the sex determination decision has been made through factors produced by the gonads that determine the development of the phenotypic sex.
    [Show full text]
  • Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome: a Comprehensive Update Morten Krogh Herlin1,2* , Michael Bjørn Petersen1,3 and Mats Brännström4
    Herlin et al. Orphanet Journal of Rare Diseases (2020) 15:214 https://doi.org/10.1186/s13023-020-01491-9 REVIEW Open Access Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: a comprehensive update Morten Krogh Herlin1,2* , Michael Bjørn Petersen1,3 and Mats Brännström4 Abstract Background: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also referred to as Müllerian aplasia, is a congenital disorder characterized by aplasia of the uterus and upper part of the vagina in females with normal secondary sex characteristics and a normal female karyotype (46,XX). Main body: The diagnosis is often made during adolescence following investigations for primary amenorrhea and hasanestimatedprevalenceof1in5000livefemalebirths.MRKH syndrome is classified as type I (isolated uterovaginal aplasia) or type II (associated with extragenital manifestations). Extragenital anomalies typically include renal, skeletal, ear, or cardiac malformations. The etiology of MRKH syndrome still remains elusive, however increasing reports of familial clustering point towards genetic causes and the use of various genomic techniques has allowed the identification of promising recurrent genetic abnormalities in some patients. The psychosexual impact of having MRKH syndrome should not be underestimated and the clinical care foremost involves thorough counselling and support in careful dialogue with the patient. Vaginal agenesis therapy is available for mature patients following therapeutical counselling and education with non-invasive vaginal dilations recommended as first-line
    [Show full text]
  • Analysis of Copy Number Variations Of
    Zhu et al. Orphanet J Rare Dis (2021) 16:258 https://doi.org/10.1186/s13023-021-01888-0 RESEARCH Open Access Analysis of copy number variations of WNT4 gene in a Chinese population with Müllerian anomalies Ying Zhu1,2,3†, Ruyi Wang4,5†, Yun Cheng1,2,3, Yang Han1,2,3, Tengyan Li5, Yunxia Cao1,2,3* and Binbin Wang4,5* Abstract Background: To investigate the genetic contribution of copy number variations (CNVs) in Wingless-type MMTV inte- gration site family, member 4 (WNT4), in a Chinese population with Müllerian anomalies (MA), copy number analysis of WNT4 by Multiplex ligation‐dependent probe amplifcation (MLPA) was performed on 248 female patients. Some studies have shown that heterozygous missense mutation of WNT4 can lead to MA. However, few studies on the relationship between WNT4 CNVs and MA have been performed. Results: Among the 248 Chinese women afected by MA in this study, heterozygous deletion of WNT4 was detected in a single patient. Conclusions: MLPA identifed one heterozygous deletion in WNT4 in a single female patient among 248 Chinese women afected by MA. This study frstly reports CNVs of WNT4 in a large sample of MA patients from the Chinese population, which suggests that CNVs of WNT4 cannot be excluded in the occurrence of MA. This provides a genetic basis for precise treatment in the future. Keywords: Copy number variations, WNT4, Müllerian anomalies, Chinese population Background for Gynaecological Endoscopy (ESHRE/ESGE) in 2013 Müllerian anomalies (MA) are among the most com- [4], Müllerian duct abnormalities can be classifed into mon diseases in gynecology and obstetrics.
    [Show full text]