OB29 : Prader-Willi syndrome originated from Uniparental Disomy(UPD) prenatally diagnosed by DNA methylation analysis and methylation specific-multiplex ligation-dependent probe amplification(MS-MLPA)

Objective: To discuss the current status of established and ongoing prenatal genetic testing options for Prader-Willi syndrome(PWS), especially if it comes from maternal unipaternal disomy(UPD), including noninvasive prenatal test(NIPT) and more detailed molecular tests. Methods: PWS, ultimately caused by lack of expression of genes from the chromosome 15 contributed by the father, has been found to be responsible for three genetic causes. Maternal UPD occurs in about 25%, while two-thirds occurred by paternally-contributed 15q11-q13 deletions and remaining by imprinting defect. Since the genetic of PWS is complicated, advent modern genetic analysis is needed to help to identify the PWS. Results: The result of Trisomy 15 in NIPT may suggests PWS with maternal UPD, while true trisomy 15 aborted in early gestations. DNA methylation analysis of chromosome 15, the method of amplifying Bi-S-treated DNA with a maternal primer capable of amplifying the methylated SNRPN(small nuclear ribonucleoprotein polypeptide-N) gene and a paternal primer capable of amplifying the unmethylated SNRPN gene, results that only the maternal allele is amplified. The methylation specific-multiplex ligation-dependent probe amplification(MS-MLPA) is a method using a restriction enzyme that can specifically cut only the unmethy DNA using the property that the maternal allele is always methylated and the paternal allele is always unmethylated among the 15 chromosomes. In Normal, the maternal allele is not truncated and the paternal allele is cut off, resulting in a ratio value of 1. SNRPN gene and NDN(necdin) gene on chromosome 15 are not cleaved into enzyme, resulting in a value twice that of normal. These results means that it is an UPD with two maternal alleles. Conclusion: With regard to complicated hereditary disorders such as UPD, accurate diagnosis with identifying precise genetic subtypes of PWS has been made by growing interest of NIPT and combination of detailed molecular genetic analysis following the abnormal NIPT results.