A girl with incomplete Prader-Willi syndrome and negative MS-PCR, found to have mosaic maternal UPD-15 at SNP array.
The Prader-Willi syndrome (PWS) is caused by lack of expression of paternal allele of the 15q11.2-q13 region, due to deletions at paternal 15q11.2-q13 (<70%), maternal uniparental disomy of chromosome 15 (mat-UPD 15) (30%) or imprinting defects (1%). Hyperphagia, intellectual disabilities/behavioral disorders, neonatal hypotonia, and hypogonadism are cardinal features for PWS. Methylation sensitive PCR (MS-PCR) of the SNRPN locus, which assesses the presence of both the unmethylated (paternal) and the methylated (maternal) allele of 15q11.2-q13, is considered a sensitive reference technique for PWS diagnosis regardless of genetic subtype. We describe a 17-year-old girl with severe obesity, short stature, and intellectual disability, without hypogonadism and history of neonatal hypotonia, who was suspected to have an incomplete PWS. The MS-PCR showed a normal pattern with similar maternal and paternal electrophoretic bands. Afterwards, a SNP array showed the presence of iso-UPD 15, that is, UPD15 with two copies of the same chromosome 15, in about 50% of cells, suggesting a diagnosis of partial PWS due to mosaic maternal iso-UPD15 arisen as rescue of a post-fertilization error. A quantitative methylation analysis confirmed the presence of mosaic UPD15 in about 50% of cells. We propose that complete clinical criteria for PWS and MS-PCR should not be considered sensitive in suspecting and diagnosing partial PWS due to mosaic UPD15. In contrast, clinical suspicion based on less restrictive criteria followed by SNP array is a more powerful approach to diagnose atypical PWS due to UPD15 mosaicism.
['Morandi|Anita|A|', 'Bonnefond|Amélie|A|', 'Lobbens|Stéphane|S|', 'Carotenuto|Marco|M|', 'Del Giudice|Emanuele Miraglia|EM|', 'Froguel|Philippe|P|', 'Maffeis|Claudio|C|']
D000293:Adolescent D000328:Adult D002648:Child D002675:Child, Preschool D002884:Chromosomes, Human, Pair 15 D019175:DNA Methylation D004587:Electrophoresis, Agar Gel D005260:Female D006801:Humans D007223:Infant D007231:Infant, Newborn D008297:Male D009030:Mosaicism D020411:Oligonucleotide Array Sequence Analysis D016133:Polymerase Chain Reaction D020641:Polymorphism, Single Nucleotide D011218:Prader-Willi Syndrome D024182:Uniparental Disomy D055517:snRNP Core Proteins
mosaic SNP array prader willi syndrome