title: Small mosaic deletion encompassing the snoRNAs and SNURF-SNRPN results in an atypical Prader-Willi syndrome phenotype.
abstract: Genetic analyses were performed in a male patient with suspected Prader-Willi syndrome who presented with hypogonadism, excessive eating, central obesity, small hands and feet and cognition within the low normal range. However, he had no neonatal hypotonia or feeding problems during infancy. Chromosome analysis showed a normal male karyotype. Further analysis with array-CGH identified a mosaic 847 kb deletion in 15q11-q13, including SNURF-SNRPN, the snoRNA gene clusters SNORD116 (HBII-85), SNORD115, (HBII-52), SNORD109 A and B (HBII-438A and B), SNORD64 (HBII-13), and NPAP1 (C15ORF2). MLPA confirmed the deletion and the results were compatible with a paternal origin. Metaphase-FISH verified the mosaicism with the deletion present in 58% of leukocytes analyzed. Three smaller deletions in this region have previously been reported in patients with Prader-Willi syndrome phenotype. All three deletions included SNORD116, but only two encompassed parts of SNURF-SNRPN, implicating SNORD116 as the major contributor to the Prader-Willi phenotype. Our case adds further information about genotype-phenotype correlation and supports the hypothesis that SNORD116 plays a major role in the pathogenesis of Prader-Willi syndrome. Furthermore, it examplifies diagnostic difficulties in atypical cases and illustrates the need for additional testing methods when Prader-Willi syndrome is suspected.
authors: Department of Molecular Medicine and Surgery, Clinal Genetic Unit, Centre of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
authors: Britt-Marie
authors: BM
authors: Anderlid
authors: Johanna
authors: J
authors: Lundin
authors: Helena
authors: H
authors: Malmgren
authors: Mikael
authors: M
authors: Lehtihet
authors: Ann
authors: A
authors: Nordgren
mesh_terms: D000328:Adult; D055028:Comparative Genomic Hybridization; D019066:Facies; D056726:Genetic Association Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D009030:Mosaicism; D005810:Multigene Family; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000175:diagnosis* / Q000235:genetics*; D020537:RNA, Small Nucleolar / Q000235:genetics*; D015203:Reproducibility of Results; D017384:Sequence Deletion
chemical_list: D009687:Nuclear Proteins; D020537:RNA, Small Nucleolar; C445239:SNURF protein, human
keywords: Prader-Willi; SNRF-SNRPN; SnoRNAs; array-CGH; atypical deletion; mosaicism