title: Prader-Willi syndrome and atypical submicroscopic 15q11-q13 deletions with or without imprinting defects.
abstract: We report a 20 year follow up on a Caucasian female, now 26 years of age, with Prader-Willi syndrome (PWS) harboring an atypical 15q11-q13 submicroscopic deletion of 100-200 kb in size first detected in 1996 involving the imprinting center, SNRPN gene and surrounding region. PWS is a rare complex disorder caused by the loss of paternally expressed genes in the 15q11-q13 region. With high resolution chromosomal microarray and methylation - specific MLPA analysis, we updated the genetic findings on our patient and found a 209,819bp deletion including the SNURF-SNRPN gene complex which includes the imprinting center and the SNORD116 region. We compared with four other similarly reported individuals in the literature with atypical submicroscopic deletions within this region but without imprinting center involvement to better characterize the specific genetic lesions causing PWS clinical findings. Clinically, our patient met the diagnostic criteria of PWS including infantile hypotonia, a poor suck with feeding difficulties, global developmental delays and later food foraging, childhood obesity, small hands and skin picking. Small atypical deletions of comparable sizes were seen in the 15q11-q13 region in all five cases and similar behavioral/physical characteristics were found despite an imprinting defect in our patient. These results further support an overlapping critical deletion region involving the non-coding snoRNA SNORD116 in common in the five individuals playing a key role in contributing to the PWS phenotype.
authors.affiliation: Department of Psychiatry & Behavioral Sciences, University of Kansas Medical Center, Kansas City, KS, USA; Department of Pediatrics, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Maaz
authors.initials: M
authors.lastname: Hassan
authors.affiliation: Department of Psychiatry & Behavioral Sciences, University of Kansas Medical Center, Kansas City, KS, USA; Department of Pediatrics, University of Kansas Medical Center, Kansas City, KS, USA. Electronic address: mbutler4@kumc.edu.
authors.forename: Merlin G
authors.initials: MG
authors.lastname: Butler
mesh_terms: D000293:Adolescent; D000328:Adult; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D018392:Genomic Imprinting / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000235:genetics* / Q000503:physiopathology; D020537:RNA, Small Nucleolar / Q000235:genetics*; D055517:snRNP Core Proteins / Q000235:genetics
chemical_list: D020537:RNA, Small Nucleolar; C000601579:SNORD116 RNA, human; C526417:SNRPN protein, human; D055517:snRNP Core Proteins
keywords: 15q11-q13 region; Atypical microdeletion; Imprinting center defect; Prader-Willi syndrome; SNORD116; SNURF-SNRPN