Detection of deletions and uniparental disomies in Prader-Willi and Angelman syndromes - methodical and interpretational aspects
Abstract
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are devastating disorders, each occuring in about 1/15000 live births and associated with significant developmental, behavioural and mental problems. These distinct clinical phenotypes are caused by a deficiency of paternal (PWS) or maternal (AS) 15q11-q13 region, which caused by the mechanism of genomic imprinting.
Authors report the results of DNA analysis of 32 patients with clinical signs of PWS and 21 patients with suspect AS by short tandem repeat (STR) analysis in locuses D15S11, D15S113 and GABRB3. In the PWS group we were able to detect seven paternal deletions and one uniparental maternal heterodisomy, and in the AS suspect population eleven maternal deletions.
The reliability of the method depends on detection of microdeletions not visible by classical cytogenetic approaches and also uniparental heterodisomic status of non-deletion patients. This method has the limitation of restricted information of the polymorphic STR systems in the family of the proband.
Due to this limitation the diagnostic system had in authors' study an efficiency of 85% in both groups.