Evaluation of Clinically Overlapping Prader-Willi and Prader-Willi-Like Syndromes Using MS-MLPA and aCGH

Objective: Prader-Willi Syndrome (PWS) is a multisystemic disorder associated with paternal deletions, maternal uniparental disomy (matUPD), and mutations in the 15q11-q13 region. Prader-Willi-Like Syndrome (PWLS) cases, although lacking alterations in this region, display similar clinical features. Genetic variations in chromosomes 1, 2, 6, 10, 12, 14 and X have been suggested to contribute to PWLS, complicating diagnosis. This study aimed to analyze methylation profiles and identify possible genetic variations in all chromosomes to differentiate PWS from PWLS.Material and Methods: Eleven cases with PWS phenotypes normal cytogenetic karyotypes, and no 15q11.2-q13 deletions were included. Methylation-Specific-Multiplex-Ligation-Dependent-Probe-Amplification (MS-MLPA) was used for methylation analysis. In cases with normal methylation, Array Comparative Genomic Hybridization (aCGH) was used to evaluate entire regions of the genome for copy number variants. Results: An abnormal methylation pattern was detected in one case. The remaining nine cases showed no changes in the 15q11.2-q13 region and were classified as PWLS. Based on aCGH analysis of these patients, we found some alterations that might be important in PWLS pathogenesis. Conclusions: PWS was identified in only one case, while the others were classified as PWLS. Some alterations that can be involved in pathogenesis of PWLS were detected by aCGH in the PWLS group but to make a clinically significant interpretation and to better understand the etiology of PWLS, all PWLS patients’ parents have to be examined by aCGH too.