title: DNA copy number variations are important in the complex genetic architecture of müllerian disorders.
abstract: OBJECTIVE
  To clinically and genetically investigate women with müllerian disorders, including Mayer-Rokitanksy-Kuster-Hauser (MRKH) syndrome.
  
  
  METHODS
  Two-year prospective clinical and laboratory study.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  Thirty-five women over 16 years of age with a müllerian disorder, including MRKH.
  
  
  METHODS
  Women were recruited from specialist gynecology clinics or identified from the Scottish Disorders of Sex Development Register (www.sdsd.scot.nhs.uk/index.html). Associated abnormalities were detected by clinical examination, imaging studies, and biochemical analyses. Chromosomal microduplications and microdeletions were detected by array comparative genomic hybridization (CGH) and validated by fluorescence in situ hydridization.
  
  
  METHODS
  Identification of associated congenital and biochemical abnormalities and identification of regions of genomic imbalance using array CGH.
  
  
  RESULTS
  Associated congenital anomalies were common, present in 25/35 (71%) of affected women, particularly renal and skeletal abnormalities, which were present in 15/35 (43%) and 17/35 (49%) women, respectively. Using array CGH, novel or recurrent regions of genomic imbalance were identified in 4/11 (36%) women with MRKH and in 5/24 (21%) women with other müllerian abnormalities.
  
  
  CONCLUSIONS
  Additional congenital abnormalities and regions of genomic imbalance are common in women with müllerian disorders, including MRKH. Recurrent microdeletions and microduplications associated with MRKH implicate specific possibly causative genes. The investigation of women with müllerian disorders should be thorough, and array CGH should be considered, given the potential highly significant familial implications of a chromosomal abnormality.
authors.affiliation: West of Scotland Clinical Genetics Service, Southern General Hospital, Glasgow, United Kingdom. Electronic address: ruthmcgowan@nhs.net.
authors.forename: Ruth
authors.initials: R
authors.lastname: McGowan
authors.affiliation: Department of Obstetrics and Gynaecology, Victoria Hospital, Kirkcaldy, United Kingdom.
authors.forename: Graham
authors.initials: G
authors.lastname: Tydeman
authors.affiliation: Department of Clinical Biochemistry, Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Shapiro
authors.affiliation: Laboratory Genetics, Southern General Hospital, Glasgow, United Kingdom.
authors.forename: Tracey
authors.initials: T
authors.lastname: Craig
authors.affiliation: Laboratory Genetics, Southern General Hospital, Glasgow, United Kingdom.
authors.forename: Norma
authors.initials: N
authors.lastname: Morrison
authors.affiliation: Department of Obstetrics and Gynaecology, National University Hospital, Singapore.
authors.forename: Susan
authors.initials: S
authors.lastname: Logan
authors.affiliation: Leeds Centre for Reproductive Medicine, Seacroft Hospital, Leeds, United Kingdom.
authors.forename: Adam H
authors.initials: AH
authors.lastname: Balen
authors.affiliation: Section of Child Health, University of Glasgow, Royal Hospital for Sick Children, Yorkhill, United Kingdom.
authors.forename: S Faisal
authors.initials: SF
authors.lastname: Ahmed
authors.affiliation: Department of Gynaecology, Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Miriam
authors.initials: M
authors.lastname: Deeny
authors.affiliation: West of Scotland Clinical Genetics Service, Southern General Hospital, Glasgow, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Tolmie
authors.affiliation: School of Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Tobias
mesh_terms: D058489:46, XX Disorders of Sex Development / Q000453:epidemiology / Q000235:genetics*; D000015:Abnormalities, Multiple / Q000453:epidemiology / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D055028:Comparative Genomic Hybridization; D000013:Congenital Abnormalities / Q000453:epidemiology / Q000235:genetics*; D020732:Cytogenetic Analysis; D056915:DNA Copy Number Variations; D012734:Disorders of Sex Development / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D009095:Mullerian Ducts / Q000002:abnormalities*; D055815:Young Adult
keywords: CNV; MRKH; Müllerian; array CGH