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

To determine gene expression of five imprinted genes or transcripts from the 15q11-q13 chromosome region using reverse transcription polymerase chain reaction (RT-PCR) in a relatively large survey of Prader-Willi syndrome (PWS) and control subjects with several different chromosome 15 abnormalities.

RT-PCR was undertaken on mRNA isolated from tissue (e.g., mostly lymphoblasts) from 38 PWS and 10 control subjects. DNA primers were used for five imprinted genes or transcripts (ZNF127, SNRPN, PAR5, IPW, and PAR1) from 15q11-q13 and fibrillin, a control gene from 15q21.

One PWS subject with maternal disomy 15 showed weak but detectable expression 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.

No obvious clinical differences were identified in those PWS subjects with weak expression of genes compared with those showing no expression. Although the reason(s) for weak expression is unknown, possible explanations include relaxation of imprinting caused by failure to reset the imprinted genes or transcripts in the maternal germ line or by postzygotic gene expression or undetected chromosome 15 mosaicism in the deletion PWS subjects. The timing, tissue source, and other factors relating to partial expression of genes that are thought to be imprinted may play a role in clinical variability and allow for a better understanding of molecular mechanisms in PWS and other abnormalities of proximal chromosome 15q.