Prader-Willi syndrome: diagnostic strategy with a cytogenetic and molecular approach

Prader-Willi syndrome (PWS) is a disorder characterized by neonatal hypotonia with poor suck, mild to moderate mental retardation, obesity beginning after 3 yr of age, hypogonadism and characteristic facial features. High resolution cytogenetic studies showed a deletion of the proximal chromosome 15q(q11-q13) region in approximately 50%. Interestingly, the same deletion was described in another distinct mental disorder: the Angelman syndrome (AS). This deletion was confirmed by molecular analyses, and a new mechanism was reported: uniparental disomy (maternal in PWS and paternal in AS) strongly implicate genomic imprinting in this chromosomal region. The principal aim of our group is to apply cytogenetic and molecular biology techniques to perform diagnosis and genetic counselling. Patient studies were usually based on high resolution cytogenetic analysis, quantitative Southern blotting (with D15S9, D15S11, D15S10, D15S12 loci) and dinucleotide repeat polymorphism assay by polymerase chain reaction (PCR) (IR4 .3R and GABARB3). The combination of these different methods allowed us to propose a diagnostic strategy for PWS.