title: Duplication of the VHL and IRAK2 genes in a patient with mental retardation/multiple congenital anomalies, epilepsy and ectomorphic habitus.
abstract: Partial 3p duplications are very rare. Often they are reported in translocations involving other chromosomes, whereas deletions encompassing the VHL gene in 3p25.3 predispose to Van-Hippel Lindau syndrome. We report here a paternally-inherited microduplication of 3p25.3 detected by array comparative genomic hybridisation (aCGH) in a 17 year-old male patient presenting with mental retardation and multiple congenital anomalies (MR/MCA), epilepsy and ectomorphic habitus. He has no tumour and there is no history of familial cancer. We refined the duplication by Multiplex Ligation-dependent Probe Amplification (MLPA) to a 251 kb region encompassing the VHL and IRAK2 genes. The duplication is likely to be causal. Interestingly, duplication of IRAK2 can cause epilepsy. Disruption of the GHRL gene can explain the ectomorphic habitus. To our knowledge, this is the smallest 3p duplication encompassing the VHL region. Its prognosis is unknown and a long-term follow-up is essential for an early diagnosis of malignancy.
authors.affiliation: Centre for Human Genetics, Hospitals of Leuven, Leuven, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Chabchoub
authors.forename: G
authors.initials: G
authors.lastname: Michils
authors.forename: J R
authors.initials: JR
authors.lastname: Vermeesch
authors.forename: P
authors.initials: P
authors.lastname: De Cock
authors.forename: L
authors.initials: L
authors.lastname: Lagae
authors.forename: J P
authors.initials: JP
authors.lastname: Fryns
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics*; D020440:Gene Duplication; D054439:Ghrelin / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D013008:Somatotypes; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*
chemical_list: D054439:Ghrelin; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D053592:Interleukin-1 Receptor-Associated Kinases; C497446:VHL protein, human