title: High incidence of recurrent copy number variants in patients with isolated and syndromic Müllerian aplasia.
abstract: BACKGROUND
  Congenital malformations involving the Müllerian ducts are observed in around 5% of infertile women. Complete aplasia of the uterus, cervix, and upper vagina, also termed Müllerian aplasia or Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, occurs with an incidence of around 1 in 4500 female births, and occurs in both isolated and syndromic forms. Previous reports have suggested that a proportion of cases, especially syndromic cases, are caused by variation in copy number at different genomic loci.
  
  
  METHODS
  In order to obtain an overview of the contribution of copy number variation to both isolated and syndromic forms of Müllerian aplasia, copy number assays were performed in a series of 63 cases, of which 25 were syndromic and 38 isolated.
  
  
  RESULTS
  A high incidence (9/63, 14%) of recurrent copy number variants in this cohort is reported here. These comprised four cases of microdeletion at 16p11.2, an autism susceptibility locus not previously associated with Müllerian aplasia, four cases of microdeletion at 17q12, and one case of a distal 22q11.2 microdeletion. Microdeletions at 16p11.2 and 17q12 were found in 4/38 (10.5%) cases with isolated Müllerian aplasia, and at 16p11.2, 17q12 and 22q11.2 (distal) in 5/25 cases (20%) with syndromic Müllerian aplasia.
  
  
  CONCLUSIONS
  The finding of microdeletion at 16p11.2 in 2/38 (5%) of isolated and 2/25 (8%) of syndromic cases suggests a significant contribution of this copy number variant alone to the pathogenesis of Müllerian aplasia. Overall, the high incidence of recurrent copy number variants in all forms of Müllerian aplasia has implications for the understanding of the aetiopathogenesis of the condition, and for genetic counselling in families affected by it.
authors.affiliation: Department of Obstetrics and Gynecology, University-Clinic Erlangen, Erlangen, Germany.
authors.forename: Serena
authors.initials: S
authors.lastname: Nik-Zainal
authors.forename: Reiner
authors.initials: R
authors.lastname: Strick
authors.forename: Mekayla
authors.initials: M
authors.lastname: Storer
authors.forename: Ni
authors.initials: N
authors.lastname: Huang
authors.forename: Roland
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authors.lastname: Rad
authors.forename: Lionel
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authors.lastname: Willatt
authors.forename: Tomas
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authors.lastname: Fitzgerald
authors.forename: Vicki
authors.initials: V
authors.lastname: Martin
authors.forename: Richard
authors.initials: R
authors.lastname: Sandford
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Carter
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Janecke
authors.forename: Stefan P
authors.initials: SP
authors.lastname: Renner
authors.forename: Patricia G
authors.initials: PG
authors.lastname: Oppelt
authors.forename: Peter
authors.initials: P
authors.lastname: Oppelt
authors.forename: Christine
authors.initials: C
authors.lastname: Schulze
authors.forename: Sara
authors.initials: S
authors.lastname: Brucker
authors.forename: Matthew
authors.initials: M
authors.lastname: Hurles
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Beckmann
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Strissel
authors.forename: Charles
authors.initials: C
authors.lastname: Shaw-Smith
mesh_terms: D058489:46, XX Disorders of Sex Development / Q000453:epidemiology / Q000235:genetics; D000015:Abnormalities, Multiple / Q000453:epidemiology / Q000235:genetics; D000293:Adolescent; D000328:Adult; D002872:Chromosome Deletion; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000453:epidemiology / Q000235:genetics; D056915:DNA Copy Number Variations; D005260:Female; D005820:Genetic Testing; D006801:Humans; D015994:Incidence; D007668:Kidney / Q000002:abnormalities; D009095:Mullerian Ducts / Q000002:abnormalities; D019170:Somites / Q000002:abnormalities; D013131:Spine / Q000002:abnormalities; D013577:Syndrome; D014599:Uterus / Q000002:abnormalities; D014621:Vagina / Q000002:abnormalities; D055815:Young Adult