PRENATAL DIAGNOSIS OF PRADER–WILLI SYNDROME USING PW71 METHYLATION ANALYSIS—UNIPARENTAL DISOMY AND THE SIGNIFICANCE OF RESIDUAL TRISOMY 15

Abstract

Chorionic villus sampling (CVS) was performed on a 38-year-old woman at 10 weeks' gestation for advanced maternal age. Two long-term cultures showed true mosaicism of cells with a normal karyotype and cells with trisomy 15. Follow-up amniocentesis showed only cells with a normal karyotype. Methylation analysis of amniocyte DNA using the probe PW71B showed a result consistent with a diagnosis of Prader-Willi syndrome. This result was confirmed using dinucleotide microsatellite polymorphism analysis, which showed that the fetus had maternal uniparental heterodisomy for chromosome 15. This report describes the use of methylation analysis for prenatal diagnosis of uniparental disomy 15 but also indicates that there is some doubt regarding the methylation status of all amniocyte samples, as one of nine controls showed hypomethylation. Fetal skin was found to show low-level mosaicism for trisomy 15, indicating a prolonged persistence of mosaic trisomy 15, which raises questions regarding the management of pregnancies found to be mosaic for trisomy 15.