This study describes the first quantitative methylation analysis of multiple CpG sites for three different GNAS DMRs using the Sequenom EpiTYPER in 35 controls, 12 PHPIb patients, 2 PHPIa patients and 2 patients without parathormone (PTH) resistance but having only hypocalcemia and hyperphosphatemia.
All patients have GNAS methylation defects typically with NESP hypermethylation versus XL and exon A/B hypomethylation while the imprinting of SNURF/SNRPN was normal. PHPIa patients showed an abnormal methylation in the three DMRs of GNAS. For the first time, a marked abnormal GNAS methylation was also found in 2 patients without PTH resistance but having hypocalcemia and hyperphosphatemia.
The Sequenom EpiTYPER proves to be very sensitive in detecting DNA methylation changes. Our analysis also suggests that GNAS imprinting defects might be more frequent and diverse than previously thought.