Bidirectional disruption of <i>GNAS</i> transcripts causes broad methylation defects in pseudohypoparathyroidism type 1B.

ABSTRACT: Pseudohypoparathyroidism type 1B (PHP1B) is a multihormone resistance disorder caused by aberrant GNAS methylation. Characteristic epigenetic changes at GNAS differentially methylated regions (DMRs), i.e., NESP, AS1, AS2, XL, and A/B, are associated with specific structural defects in different autosomal dominant PHP1B (AD-PHP1B) subtypes. However, mechanisms underlying abnormal GNAS methylation remain incompletely defined, largely because viable PHP1B mouse models are lacking. Using lymphoblastoid cells and induced pluripotent stem cells, we show that various GNAS methylation patterns in PHP1B reflect differential disruption of sense and antisense GNAS transcripts. In cases with broad GNAS methylation changes, loss of the maternal, sense-transcrib

SUBMITTER: Iwasaki Y 

PROVIDER: S-EPMC12037034 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature