Array comparative genomic hybridization (aCGH) analysis in Prader-Willi syndrome

• Published in: American journal of medical genetics. Part A Vol. 146A; no. 7; pp. 854 - 860
• Main Authors: Butler, Merlin G., Fischer, William, Kibiryeva, Nataliya, Bittel, Douglas C.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2008; Wiley-Liss
• Subjects: Adolescent; Adult; array comparative genomic hybridization (aCGH); Biological and medical sciences; chromosomal breakpoint; Chromosome aberrations; Chromosome Deletion; Chromosomes, Human, Pair 15; Complex syndromes; copy number variation (CNV); Female; Humans; In Situ Hybridization, Fluorescence; Male; Medical genetics; Medical sciences; Metabolic diseases; Nucleic Acid Hybridization; Obesity; Prader-Willi syndrome (PWS); Prader-Willi Syndrome - genetics; type I and II deletions; Chromosomal aberration; Endocrinopathy; Breakpoint; array comparative genomic hybridization (aCGH); Copy number; Diseases of the osteoarticular system; Variations; Genetic disease; chromosomal breakpoint; Chromosome break; Comparative genomic hybridization; Deletion; copy number variation (CNV); type I and II deletions; Complex syndrome; Prader Labhart Willi syndrome; Prader-Willi syndrome (PWS)
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.32249

Prader–Willi syndrome (PWS) is due to loss of paternally expressed genes in the 15q11–q13 region generally from a paternal 15q11–q13 deletion. The proximal deletion breakpoint in the 15q11–q13 region occurs at one of two sites located within either of two large duplicons allowing for identification of two typical deletion subgroups. The larger type I (TI) deletion involving breakpoint 1 (BP1) is nearer to the centromere and located proximal to the microsatellite marker D15S1035, while the smaller type II (TII) deletion involves breakpoint 2 (BP2) and distal to D15S1035. Breakpoint 3 (BP3) is located at the distal end of the 15q11–q13 region and common to both typical deletion subgroups. Using high resolution aCGH, BP1 spanned a region from 18.683 to 20.220 Mb, BP2 from 20.812 to 21.357 Mb and BP3 from 25.941 to 27.286 Mb. The TI deletion ranged in size from 5.721 to 8.147 Mb (mean 6.583) and the type II deletion from 4.770 to 6.435 Mb (mean 5.330). A subset of the TI subjects showed larger deletions including the loss of at least three genes/transcripts (i.e., LOC283755, POTE5, OR4N4) in addition to the four genes between BP1 and BP2 (i.e., GCP5, CYFIP1, NIPA1, NIPA2). Interestingly, four PWS subjects had duplications of the 15q11 region in addition to the typical deletion. Furthermore, most PWS subjects had copy number variation (CNV) of 50 kb or larger in other chromosome regions; most common were deletions and duplications of 8p and 3q, previously recognized sites of CNV in the human genome. © 2008 Wiley‐Liss, Inc.