Analysis of imprinted genes in subjects with Prader-Willi syndrome and chromosome 15 abnormalities

Purpose: To determine gene expression of five imprinted genes or transcript s from the 15q11-q13 chromosome region using reverse transcription polymera se chain reaction (RT-PCR) in a relatively large survey of Prader-Willi syn drome (PWS) and control subjects with several different chromosome 15 abnor malities. Methods: RT-PCR was undertaken on mRNA isolated from tissue (e.g. , mostly lymphoblasts) from 38 PWS and 10 control subjects. DNA primers wer e used for five imprinted genes or transcripts (ZNF127, SNRPN, PAR5, IPW, a nd PAR1) from 15q11-q13 and fibrillin, a control gene from 15q21. Results: One PWS subject with maternal disomy 15 showed weak but detectable expressi on of PAR1, whereas SNRPN expression was detected in two PWS subjects [one with the 15q11-q13 deletion and one with a t(15;15) karyotype and maternal disomy 15], and the remaining typical PWS subjects showed no expression of the imprinted genes or transcripts. Conclusion: No obvious clinical differe nces were identified in those PWS subjects with weak expression of genes co mpared with those showing no expression. Although the reason(s) for weak ex pression is unknown, possible explanations include relaxation of imprinting caused by failure to reset the imprinted genes or transcripts in the mater nal germ line or by postzygotic gene expression or undetected chromosome 15 mosaicism in the deletion PWS subjects. The timing, tissue source, and oth er factors relating to partial expression of genes that are thought to be i mprinted may play a role in clinical variability and allow for a better und erstanding of molecular mechanisms in PWS and other abnormalities of proxim al chromosome 15q.