title: Detailed phenotype-genotype study in five patients with chromosome 6q16 deletion: narrowing the critical region for Prader-Willi-like phenotype.
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 100 Kb 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 4.1 Mb 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.
authors.affiliation: Scientific Institute E Medea, Bosisio Parini, Lecco, Italy. clara.bonaglia@bp.lnf.it
authors.forename: Maria Clara
authors.initials: MC
authors.lastname: Bonaglia
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccone
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gimelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Gimelli
authors.forename: Susan
authors.initials: S
authors.lastname: Marelli
authors.forename: Joke
authors.initials: J
authors.lastname: Verheij
authors.forename: Roberto
authors.initials: R
authors.lastname: Giorda
authors.forename: Rita
authors.initials: R
authors.lastname: Grasso
authors.forename: Renato
authors.initials: R
authors.lastname: Borgatti
authors.forename: Filomena
authors.initials: F
authors.lastname: Pagone
authors.forename: Laura
authors.initials: L
authors.lastname: Rodrìguez
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: Martinez-Frias
authors.forename: Conny
authors.initials: C
authors.lastname: van Ravenswaaij
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D020732:Cytogenetic Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000235:genetics*