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Genomic imbalances associated with müllerian aplasia
  1. C Cheroki1,
  2. A C V Krepischi-Santos1,
  3. K Szuhai2,
  4. V Brenner3,
  5. C A E Kim4,
  6. P A Otto1,
  7. C Rosenberg1
  1. 1
    Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, Brazil
  2. 2
    Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands
  3. 3
    Oxford Gene Technology, Begbroke Science Park, Oxford, UK
  4. 4
    Genetics Unit, Department of Pediatrics, Children Institute, University of São Paulo, São Paulo, Brazil
  1. Dr C Rosenberg, Departamento de Genética e Biologia Evolutiva, IB, USP, Rua do Matão, 277, 2° andar, sala 337, 05422-970, São Paulo, SP, Brazil; carlarosenberg{at}


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 ∼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.

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  • Funding: This study was supported by grants from the State of São Paulo Foundation for Support of Research (FAPESP/CEPID 98/14254-2) and the Brazilian National Research Council (CNPq).

  • Competing interests: None declared.

  • Patient consent: Informed consent was obtained for publication of the patients’ details in this report

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