De novo interstitial duplication of 15q11.2-q13.1 with complex maternal uniparental trisomy for the 15q11-q13 region in a patient with Prader-Willi syndrome

Am J Med Genet A. 2012 Oct;158A(10):2557-63. doi: 10.1002/ajmg.a.35549. Epub 2012 Aug 17.


Prader-Willi syndrome is caused by the lack of paternal contribution for the imprinted 15q11-q13 region that originates through a number of mechanisms such as paternal deletion of 15q11-q13, maternal uniparental disomy, or by an imprinting defect due to epimutations in the paternal imprinting center. In the present report, we describe a female patient with complex maternal uniparental trisomy for the 15q11-q13 Prader-Willi syndrome critical region due to a de novo interstitial duplication of 15q11-q13 region that is present in one of the maternal homologs. As a result, the patient has three maternally derived copies of the Prader-Willi syndrome critical region and absence of paternal 15 contribution and thus, presents with a Prader-Willi syndrome phenotype with risk for developing additional phenotypes (e.g., autism and psychiatric phenotypes) characteristic of maternally derived duplications of this region. We suggest that this is a rather unique mechanism leading to Prader-Willi syndrome that has not been previously reported.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Chromosomes, Human, Pair 15 / genetics*
  • DNA Copy Number Variations / genetics*
  • Female
  • Humans
  • Infant
  • Phenotype
  • Prader-Willi Syndrome / genetics*
  • Prader-Willi Syndrome / physiopathology
  • Trisomy / genetics*
  • Uniparental Disomy / genetics*