[Pseudopseudohypoparathyroidism and genomic imprinting]

Pseudopseudohypoparathyroidism (PPHP) is caused by the paternally-derived mutation in the coding region of GNAS gene. The phenotype of PPHP is produced by the sum of both decreased Gsalpha protein in biallelically expressed tissues and other proteins or non-coding RNAs by mutated paternal-allele specific expression. It has been believed that the haploinsufficiency of Gsalpha in non-imprinted tissues is responsible for the Albright hereditary dystrophy (AHO) phenotype. Recently it was reported that obesity is a more prominent feature in pseudohypoparathyroidism type I a than in PPHP. This result implicates paternal imprinting in the development of obesity in pseudohypoparathyroidism type I a. In this review, recent advances in clinical and experimental knowledge in genomic imprinting of GNAS gene were summarized.