The investigation of methylation and uniparental disomy (UPD) of cases having clinical findings of prader-willi syndrome but with normal karyotype

Objective: Prader-Willi Syndrome (PWS) is a multisystemic disease characterized by clinical phenotypic abnormalities, cognitive impairment, and neurometabolic changes. Genetically, it is associated with the defect of genes localized in the q11-q13 region of chromosome 15. While paternal chromosome of this region is active in healthy individuals, maternal chromosome is imprinted. Disruption of the expression mechanism of the paternal genes causes PWS. Chromosomal changes in different chromosomes can also cause clinical signs of PWS. Therefore, this situation affects the correct diagnosis of the disease and it is a problem in determining when and which molecular test will be wanted by the clinicians. In this study, we aimed to provide the genotype-phenotype correlation by performing MS-MLPA in cases having clinical signs of PWS; to differentiate between PWS and Prader-Willi-Like Syndrome on a molecular basis; to provide accurate diagnosis, proper genetic counseling and appropriate treatment. Method: 12 cases having clinical signs of PWS, normal karyotype and no deletion on 15q11-q13 region confirmed by FISH, were included in the study. Methylation analysis of 15q11.2-q13 was performed by MS-MLPA method; microsatellite analysis for evaluating UPD was performed in cases having abnormal methylation pattern. The results were evaluated by comparing current literature and databases. Results: Abnormal methylation pattern was observed in 1 of 12 cases and microsatellite analysis was performed to understand the mechanism of abnormal methylation. In this case, abnormal methylation pattern was determined to be related to UPD. In 11 cases, no genetic changes were observed on 15q11.2-q13 region Conclusion: No chromosomal and genetic changes in 11 cases showed that these cases were included in Prader-Willi-Like Syndrome. To understand the etiology of the disease, to provide accurate diagnosis and genetic counseling studies with a larger group of patients are required. Key words: prader-willi syndrome, ms-mlpa, methylation profile of 15q11.2-q13, prader-willi like syndrome, upd