Rapid Diagnosis of Imprinting Disorders Involving Copy Number Variation and Uniparental Disomy Using Genome-Wide SNP Microarrays.

Abstract

Imprinting disorders, such as Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS) and Angelman syndrome (AS), can be detected via methylation analysis, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), or other methods. In this study, we applied single nucleotide polymorphism (SNP)-based chromosomal microarray analysis to detect copy number variations (CNVs) and uniparental disomy (UPD) events in patients with suspected imprinting disorders. Of 4 patients, 2 had a 5.25-Mb microdeletion in the 15q11.2q13.2 region, 1 had a 38.4-Mb mosaic UPD in the 11p15.4 region, and 1 had a 60-Mb detectable UPD between regions 14q13.2 and 14q32.13. Although the 14q32.2 region was classified as normal by SNP array for the 14q13 UPD patient, it turned out to be a heterodisomic UPD by short tandem repeat marker analysis. MS-MLPA analysis was performed to validate the variations. In conclusion, SNP-based microarray is an efficient alternative method for quickly and precisely diagnosing PWS, AS, BWS, and other imprinted gene-associated disorders when considering aberrations due to CNVs and most types of UPD.

• Authors: Weiqiang Liu, Rui Zhang, Jun Wei, Huimin Zhang, Guojiu Yu, Zhihua Li, Min Chen, Xiaofang Sun
• Journal: Cytogenetic and genome research (Cytogenet Genome Res) Vol. 146 Issue 1 Pg. 9-18 ( 2015) ISSN: 1424-859X [Electronic] Switzerland
• PMID: 26184742 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel.

Topics

• Angelman Syndrome (diagnosis, genetics)
• Beckwith-Wiedemann Syndrome (diagnosis, genetics)
• Child
• Chromosomes, Human, Pair 14 (genetics)
• Chromosomes, Human, Pair 15 (genetics)
• DNA Copy Number Variations
• Genomic Imprinting
• Humans
• Infant, Newborn
• Male
• Molecular Diagnostic Techniques
• Oligonucleotide Array Sequence Analysis
• Polymorphism, Single Nucleotide
• Prader-Willi Syndrome (diagnosis, genetics)
• Sequence Deletion
• Uniparental Disomy (diagnosis, genetics)