Detailed phenotype-genotype study in five patients with chromosome 6q16 deletion: Narrowing the critical region for Prader-Willi-like phenotype

Maria Clara Bonaglia, Roberto Ciccone, Giorgio Gimelli, Stefania Gimelli, Susan Marelli, Joke Verheij, Roberto Giorda, Rita Grasso, Renato Borgatti, Filomena Pagone, Laura Rodrìguez, Maria Luisa Martinez-Frias, Conny van Ravenswaaij, Orsetta Zuffardi

Research output: Contribution to journalArticle

Abstract

Most patients with an interstitial deletion of 6q16 have Prader-Willi-like phenotype, featuring obesity, hypotonia, short hands and feet, and developmental delay. In all reported studies, the chromosome rearrangement was detected by karyotype analysis, which provides an overview of the entire genome but has limited resolution. Here we describe a detailed clinical presentation of five patients, two of whom were previously reported, with overlapping interstitial 6q16 deletions and Prader-Willi-like phenotype. Our patients share the following main features with previously reported cases: global developmental delay, hypotonia, obesity, hyperphagia, and eye/vision anomalies. All rearrangement breakpoints have been accurately defined through array-CGH at about 100Kb resolution. We were able to narrow the shortest region of deletion overlap for the presumed gene(s) involved in the Prader-Willi-like syndrome to 4.1Mb located at 6q16.1q16.2. Our results support the evidence that haploinsufficiency of the SIM1 gene is responsible for obesity in these patients. A possible involvement of the GRIK2 gene in autistic-like behaviour, of POPDC3 in heart development, and of MCHR2 in the control of feeding behaviour and energy metabolism is also hypothesized.

Original languageEnglish
Pages (from-to)1443-1449
Number of pages7
JournalEuropean Journal of Human Genetics
Volume16
Issue number12
DOIs
Publication statusPublished - 2008

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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    Bonaglia, M. C., Ciccone, R., Gimelli, G., Gimelli, S., Marelli, S., Verheij, J., Giorda, R., Grasso, R., Borgatti, R., Pagone, F., Rodrìguez, L., Martinez-Frias, M. L., van Ravenswaaij, C., & Zuffardi, O. (2008). Detailed phenotype-genotype study in five patients with chromosome 6q16 deletion: Narrowing the critical region for Prader-Willi-like phenotype. European Journal of Human Genetics, 16(12), 1443-1449. https://doi.org/10.1038/ejhg.2008.119