Clinical Utility of Methylation-Specific Multiplex Ligation-Dependent Probe Amplification for the Diagnosis of Prader–Willi Syndrome and Angelman Syndrome

• Published in: Annals of laboratory medicine Vol. 42; no. 1; pp. 79 - 88
• Main Authors: Kim, Boram, Park, Yongsook, Cho, Sung Im, Kim, Man Jin, Chae, Jong-Hee, Kim, Ji Yeon, Seong, Moon-Woo, Park, Sung Sup
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society for Laboratory Medicine 01.01.2022; 대한진단검사의학회
• Subjects: Angelman Syndrome - diagnosis; Angelman Syndrome - genetics; Chromosomes, Human, Pair 15 - genetics; DNA Methylation; Humans; Methylation; Multiplex Polymerase Chain Reaction; Original; Prader-Willi Syndrome - diagnosis; Prader-Willi Syndrome - genetics; Retrospective Studies; 병리학; Angelman syndrome; Utility; Diagnosis; Methylation-specific PCR; Prader-Willi syndrome; Methylation-specific multiplex ligation-dependent probe amplification
• ISSN: 2234-3806; 2234-3814; 2234-3814
• DOI: 10.3343/alm.2022.42.1.79

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are genomic imprinting disorders that are mainly caused by a deletion on 15q11-q13, the uniparental disomy of chromosome 15, or an imprinting defect. We evaluated the utility of methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as a diagnostic tool and for demonstrating the relationship between molecular mechanisms and clinical presentation. We performed MS-MLPA using DNA samples from 93 subjects (45 PWS, 24 AS, and 24 non-PWS/AS controls) who had previously undergone MS-PCR for the diagnosis of PWS/AS. We compared the results of both assays, and patients' clinical phenotypes were reviewed retrospectively. MS-MLPA showed a 100% concordance rate with MS-PCR. Among the 45 PWS patients, 26 (57.8%) had a deletion of 15q11-q13, and the others (42.2%) had uniparental disomy 15 or an imprinting defect. Among the 24 AS patients, 16 (66.7%) had a deletion of 15q11-q13, 7 AS patients (29.2%) had uniparental disomy 15 or an imprinting defect, and one AS patient (4.2%) showed an imprinting center deletion. MS-MLPA has clinical utility for the diagnosis of PWS/AS, and it is superior to MS-PCR in that it can identify the molecular mechanism underlying the disease.