Lack of GNAS re-methylation during oogenesis may be a cause of sporadic pseudohypoparathyroidism type Ib (PHP1B).

Sporadic and IVF/ICSI-conceived PHP1B patients revealed indistinguishable epigenetic changes at all four GNAS DMRs thus suggesting a similar underlying disease mechanism. Given that re-methylation at the three maternal DMRs occurs during oogenesis, male factors are unlikely to cause LOM post-fertilization. Instead, at least some of the sporPHP1B variants could be caused by a defect(s) in an oocyte-expressed gene that is required for fertility and for re-establishing maternal GNAS methylation imprints. It remains uncertain, however, whether lack of GNAS re-methylation alone impairs oocyte maturation because of insufficient Gsα expression, thus necessitating Assisted Reproductive Technology (ART) for conception.