Abstract
Abstract
Background: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are well-characterised conditions in which the phenotypes and genes responsible are distinct, but they share a common genetic mechanism. PWS is due to a lack of paternally-expressed genes located to human chromosome region 15q11-q13, and AS is due to a lack of maternally-expressed genes located to the same region. There are a variety of testing strategies available to determine if a patient has either of these syndromes.
Methods and results: In this study, we tested two of the methods used in clinical laboratories to confirm a diagnosis of PWS and AS: methylation sensitive PCR (MS-PCR) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). Thirty samples which had previously been tested for either PWS or AS by MS-PCR were blinded and tested prospectively by MS-MLPA.
Conclusions: Both tests showed complete concordance with respect to confirming a clinical diagnosis. Of the three principal mutation mechanisms underpinning PWS/AS, MS-PCR cannot resolve any of them while MS-MLPA can detect deletion events; neither can differentiate between uniparental disomy or point mutations in the imprinting centre. Both techniques provide an accurate confirmation of a clinical diagnosis with the possibility of a quick turnaround time of approximately two days. Therefore, either technique would be of benefit in a routine diagnostic laboratory.