Your browser doesn't support javascript.
loading
Perturbations of genes essential for Müllerian duct and Wölffian duct development in Mayer-Rokitansky-Küster-Hauser syndrome.
Chen, Na; Zhao, Sen; Jolly, Angad; Wang, Lianlei; Pan, Hongxin; Yuan, Jian; Chen, Shaoke; Koch, André; Ma, Congcong; Tian, Weijie; Jia, Ziqi; Kang, Jia; Zhao, Lina; Qin, Chenglu; Fan, Xin; Rall, Katharina; Coban-Akdemir, Zeynep; Chen, Zefu; Jhangiani, Shalini; Liang, Ze; Niu, Yuchen; Li, Xiaoxin; Yan, Zihui; Wu, Yong; Dong, Shuangshuang; Song, Chengcheng; Qiu, Guixing; Zhang, Shuyang; Liu, Pengfei; Posey, Jennifer E; Zhang, Feng; Luo, Guangnan; Wu, Zhihong; Su, Jianzhong; Zhang, Jianguo; Chen, Eugenia Y; Rouskas, Konstantinos; Glentis, Stavros; Bacopoulou, Flora; Deligeoroglou, Efthymios; Chrousos, George; Lyonnet, Stanislas; Polak, Michel; Rosenberg, Carla; Dingeldein, Irene; Bonilla, Ximena; Borel, Christelle; Gibbs, Richard A; Dietrich, Jennifer E; Dimas, Antigone S.
Afiliação
  • Chen N; Department of Obstetrics and Gynaecology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
  • Zhao S; Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 1
  • Jolly A; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; M.D./Ph.D. Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA.
  • Wang L; Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 1
  • Pan H; Department of Obstetrics and Gynaecology, The 3rd Affiliated Hospital of Shenzhen University, Luohu hospital, Shenzhen, Guangdong 518000, China.
  • Yuan J; Institute of Biomedical Big Data, Wenzhou Medical University, Wenzhou 325027, China.
  • Chen S; Department of Pediatrics, the Second Affiliated Hospital of Guangxi Medical University, Guangxi 530003, China.
  • Koch A; Department of Gynecology and Obstetrics, Research Centre for Women's Health, Tübingen University Hospital, Tübingen 72076, Germany.
  • Ma C; Department of Obstetrics and Gynaecology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
  • Tian W; Department of Obstetrics and Gynaecology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
  • Jia Z; Department of Obstetrics and Gynaecology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
  • Kang J; Department of Obstetrics and Gynaecology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
  • Zhao L; Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 1
  • Qin C; Department of Obstetrics and Gynaecology, The 3rd Affiliated Hospital of Shenzhen University, Luohu hospital, Shenzhen, Guangdong 518000, China.
  • Fan X; Department of Pediatrics, the Second Affiliated Hospital of Guangxi Medical University, Guangxi 530003, China.
  • Rall K; Department of Gynecology and Obstetrics, Research Centre for Women's Health, Tübingen University Hospital, Tübingen 72076, Germany.
  • Coban-Akdemir Z; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Chen Z; Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 1
  • Jhangiani S; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Liang Z; Department of Obstetrics and Gynaecology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
  • Niu Y; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China.
  • Li X; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China.
  • Yan Z; Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 1
  • Wu Y; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China.
  • Dong S; Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), School of Life Sciences, Shanghai 200011, China.
  • Song C; Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), School of Life Sciences, Shanghai 200011, China.
  • Qiu G; Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 1
  • Zhang S; Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
  • Liu P; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Genetics, Houston, TX 77021, USA.
  • Posey JE; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Zhang F; Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), School of Life Sciences, Shanghai 200011, China.
  • Luo G; Department of Obstetrics and Gynaecology, The 3rd Affiliated Hospital of Shenzhen University, Luohu hospital, Shenzhen, Guangdong 518000, China.
  • Wu Z; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China; Key laboratory of big data for spinal deformities, Chinese Academy of Medical Sciences, Beijing 100730, China; Medical Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Ch
  • Su J; Institute of Biomedical Big Data, Wenzhou Medical University, Wenzhou 325027, China.
  • Zhang J; Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 1
  • Chen EY; Baylor College of Medicine, Houston, TX 77030, USA; Departments of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Obstetrics and Gynecology, Texas Children's Hospital and Baylor College of Medicine, Houston, TX 77030, USA.
  • Rouskas K; Institute for Bioinnovation, Biomedical Sciences Research Center Al. Fleming, Vari, Athens 16672, Greece; Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thermi, Thessaloniki 57001, Greece.
  • Glentis S; Institute for Bioinnovation, Biomedical Sciences Research Center Al. Fleming, Vari, Athens 16672, Greece; Division of Pediatric Hematology/Oncology, First Department of Pediatrics, University of Athens, Aghia Sophia Children's Hospital, Athens 11527, Greece.
  • Bacopoulou F; Center for Adolescent Medicine and UNESCO Chair on Adolescent Health Care, First Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital, Athens 11527, Greece.
  • Deligeoroglou E; Division of Pediatric-Adolescent Gynecology and Reconstructive Surgery, 2(nd) Department of Obstetrics and Gynecology, School of Medicine, National and Kapodistrian University of Athens, Aretaieion Hospital, Athens 10679, Greece.
  • Chrousos G; Center for Adolescent Medicine and UNESCO Chair on Adolescent Health Care, First Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital, Athens 11527, Greece.
  • Lyonnet S; Institut Imagine, UMR-1163 INSERM et Universite de Paris, Hospital Universitaire Necker-Enfants Malades, Paris 75015, France.
  • Polak M; Institut Imagine, UMR-1163 INSERM et Universite de Paris, Hospital Universitaire Necker-Enfants Malades, Paris 75015, France.
  • Rosenberg C; Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of Sao Paulo, Sao Paulo 05508-090, Brazil.
  • Dingeldein I; Inselspital FrauenKlinik, University of Bern, Bern 3012, Switzerland.
  • Bonilla X; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva 1205, Switzerland.
  • Borel C; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva 1205, Switzerland.
  • Gibbs RA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Human Genome Seuencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Dietrich JE; Departments of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Obstetrics and Gynecology, Texas Children's Hospital and Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA.
  • Dimas AS; Institute for Bioinnovation, Biomedical Sciences Research Center Al. Fleming, Vari, Athens 16672, Greece.
Am J Hum Genet ; 108(2): 337-345, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33434492
ABSTRACT
Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait. Disrupted development of the Müllerian ducts (MD)/Wölffian ducts (WD) through multifactorial mechanisms has been proposed to underlie MRKHS. In this study, exome sequencing (ES) was performed on a Chinese discovery cohort (442 affected subjects and 941 female control subjects) and a replication MRKHS cohort (150 affected subjects of mixed ethnicity from North America, South America, and Europe). Phenotypic follow-up of the female reproductive system was performed on an additional cohort of PAX8-associated congenital hypothyroidism (CH) (n = 5, Chinese). By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting (LGD) variants in 7 genes PAX8 (n = 4), BMP4 (n = 2), BMP7 (n = 2), TBX6 (n = 1), HOXA10 (n = 1), EMX2 (n = 1), and WNT9B (n = 1), while LGD variants in these genes were not detected in control samples (p = 1.27E-06). Interestingly, a sex-limited penetrance with paternal inheritance was observed in multiple families. One additional PAX8 LGD variant from the replication cohort and two missense variants from both cohorts were revealed to cause loss-of-function of the protein. From the PAX8-associated CH cohort, we identified one individual presenting a syndromic condition characterized by CH and MRKHS (CH-MRKHS). Our study demonstrates the comprehensive utilization of knowledge from developmental biology toward elucidating genetic perturbations, i.e., rare pathogenic alleles involving the same loci, contributing to human birth defects.
Assuntos
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Anormalidades Congênitas / Ductos Mesonéfricos / Transtornos 46, XX do Desenvolvimento Sexual / Ductos Paramesonéfricos / Mutação Limite: Adulto / Feminino / Humanos Idioma: Inglês Revista: Am J Hum Genet Ano de publicação: 2021 Tipo de documento: Artigo País de afiliação: China

Similares

MEDLINE

...
LILACS

LIS

Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Anormalidades Congênitas / Ductos Mesonéfricos / Transtornos 46, XX do Desenvolvimento Sexual / Ductos Paramesonéfricos / Mutação Limite: Adulto / Feminino / Humanos Idioma: Inglês Revista: Am J Hum Genet Ano de publicação: 2021 Tipo de documento: Artigo País de afiliação: China