Genomic imbalances associated with mullerian aplasia

J Med Genet. 2008 Apr;45(4):228-32. doi: 10.1136/jmg.2007.051839. Epub 2007 Nov 26.


Background: Aplasia of the müllerian ducts leads to absence of the uterine corpus, uterine cervix, and upper (superior) vagina. Patients with müllerian aplasia (MA) often exhibit additional clinical features such as renal, vertebral and cardiac defects. A number of different syndromes have been associated with MA, and in most cases its aetiology remains poorly understood.

Objective and methods: 14 syndromic patients with MA and 46,XX G-banded karyotype were screened for DNA copy number changes by approximately 1 Mb whole genome bacterial artificial chromosome (BAC) array based comparative genomic hybridisation (CGH). The detected alterations were validated by an independent method and further mapped by high resolution oligo-arrays.

Results: Submicroscopic genomic imbalances affecting the 1q21.1, 17q12, 22q11.21, and Xq21.31 chromosome regions were detected in four probands. Presence of the alterations in the normal mother of one patient suggests incomplete penetrance and/or variable expressivity.

Conclusion: 4 of the 14 patients (29%) were found to have cryptic genomic alterations. The imbalances on 22q11.21 support recent findings by us and others that alterations in this chromosome region may result in impairment of müllerian duct development. The remaining imbalances indicate involvement of previously unknown chromosome regions in MA, and point specifically to LHX1 and KLHL4 as candidate genes.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Adolescent
  • Adult
  • Allelic Imbalance*
  • Child, Preschool
  • Chromosome Aberrations*
  • Chromosome Deletion
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 17 / genetics
  • Chromosomes, Human, Pair 22 / genetics
  • Chromosomes, Human, X / genetics
  • Cytoskeletal Proteins / genetics
  • Female
  • Gene Dosage
  • Genitalia, Female / abnormalities*
  • Homeodomain Proteins / genetics
  • Humans
  • LIM-Homeodomain Proteins
  • Middle Aged
  • Mullerian Ducts / abnormalities*
  • Nucleic Acid Hybridization
  • Syndrome
  • Transcription Factors
  • Uterus / abnormalities
  • Vagina / abnormalities
  • Wnt Proteins / genetics
  • Wnt4 Protein


  • Cytoskeletal Proteins
  • Homeodomain Proteins
  • KLHL4 protein, human
  • LHX1 protein, human
  • LIM-Homeodomain Proteins
  • Transcription Factors
  • WNT4 protein, human
  • Wnt Proteins
  • Wnt4 Protein