Chromosomal Microarray Study in Prader-Willi Syndrome

Abstract

A high-resolution chromosome microarray analysis was performed on 154 consecutive individuals enrolled in the DESTINY PWS clinical trial for Prader-Willi syndrome (PWS). Of these 154 PWS individuals, 87 (56.5%) showed the typical 15q11-q13 deletion subtypes, 62 (40.3%) showed non-deletion maternal disomy 15 and five individuals (3.2%) had separate unexpected microarray findings. For example, one PWS male had Klinefelter syndrome with segmental isodisomy identified in both chromosomes 15 and X. Thirty-five (40.2%) of 87 individuals showed typical larger 15q11-q13 Type I deletion and 52 individuals (59.8%) showed typical smaller Type II deletion. Twenty-four (38.7%) of 62 PWS individuals showed microarray patterns indicating either maternal heterodisomy 15 subclass or a rare non-deletion (epimutation) imprinting center defect. Segmental isodisomy 15 was seen in 34 PWS subjects (54.8%) with 15q26.3, 15q14 and 15q26.1 bands most commonly involved and total isodisomy 15 seen in four individuals (6.5%). In summary, we report on PWS participants consecutively enrolled internationally in a single clinical trial with high-resolution chromosome microarray analysis to determine and describe an unbiased estimate of the frequencies and types of genetic defects and address potential at-risk genetic disorders in those with maternal disomy 15 subclasses in the largest PWS cohort studied to date.

Behavioral and Psychiatric Disorders in Syndromic Autism

“…There are two deletion types in PWS, the larger Type I and smaller Type II. The remaining affected individuals have either a defect in the imprinting center controlling the imprinted genes in the PWCR or chromosome 15 translocations or inversions [60][61][62]. The diagnosis and molecular cause of PWS can be identified using high-resolution chromosome microarrays [61] or, more precisely, with a streamlined molecular approach including whole-exome sequencing with a deletion or duplication status, and DNA methylation analysis with methylation-sensitive multiplex ligation-dependent probe amplification (MS-MLPA) [63].…”