Methylation, cytogenetic and FISH tests in the molecular diagnosis of Prader-Willi and Angelman syndromes

Background: The diagnosis of Prader-Willi and Angelman syndromes is difficu lt, since their phenotypic manifestations are variable and unspecific. The study of the methylation state of DNA in 15 (q11-q13) using polymerase chai n reaction, called methylation test, allows the diagnosis of most patients with Prader-Willi and Angelman syndromes, irrespective if the underlying mo lecular alteration is a deletion, uniparental disomy or a punctual imprinti ng mutation. Aim: To assess the effectiveness of methylation test in the di agnosis of Prader-Willi and Angelman syndromes. Patients and methods: Thirt y seven cases with a presumptive diagnosis of Prader-Willi syndrome and 25 with the presumptive diagnosis of Angelman syndrome were studied. Methylati on test was done in genomic DNA obtained from peripheral lymphocytes. Resul ts: Methylation test confirmed the clinical diagnosis in 11 of 37 patients with PraderWilli (30%) and 6 of 25 patients with Angelman syndrome (24%). C onclusions: Clinical criteria overestimate the diagnosis of Prader-Willi an d Angelman syndromes. The initial diagnosis should be confirmed with the me thylation test and if necessary with FISH that will detect most deletions i n the region.