title: Unique and atypical deletions in Prader-Willi syndrome reveal distinct phenotypes.
abstract: Prader-Willi syndrome (PWS) is a multisystem, contiguous gene disorder caused by an absence of paternally expressed genes within the 15q11.2-q13 region via one of the three main genetic mechanisms: deletion of the paternally inherited 15q11.2-q13 region, maternal uniparental disomy and imprinting defect. The deletion class is typically subdivided into Type 1 and Type 2 based on their proximal breakpoints (BP1-BP3 and BP2-BP3, respectively). Despite PWS being a well-characterized genetic disorder the role of the specific genes contributing to various aspects of the phenotype are not well understood. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) is a recently developed technique that detects copy number changes and aberrant DNA methylation. In this study, we initially applied MS-MLPA to elucidate the deletion subtypes of 88 subjects. In our cohort, 32 had a Type 1 and 49 had a Type 2 deletion. The remaining seven subjects had unique or atypical deletions that were either smaller (n=5) or larger (n=2) than typically described and were further characterized by array-based comparative genome hybridization. In two subjects both the PWS region (15q11.2) and the newly described 15q13.3 microdeletion syndrome region were deleted. The subjects with a unique or an atypical deletion revealed distinct phenotypic features. In conclusion, unique or atypical deletions were found in ∼8% of the deletion subjects with PWS in our cohort. These novel deletions provide further insight into the potential role of several of the genes within the 15q11.2 and the 15q13.3 regions.
authors: Department of Psychiatry, University of Florida, Gainesville, FL, USA.
authors: Soo-Jeong
authors: SJ
authors: Kim
authors: Jennifer L
authors: JL
authors: Miller
authors: Paul J
authors: PJ
authors: Kuipers
authors: Jennifer Ruth
authors: JR
authors: German
authors: Arthur L
authors: AL
authors: Beaudet
authors: Trilochan
authors: T
authors: Sahoo
authors: Daniel J
authors: DJ
authors: Driscoll
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D005260:Female; D023061:Gene Order; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000175:diagnosis / Q000235:genetics*; D015203:Reproducibility of Results; D055815:Young Adult