Deletion of the noncoding GNAS antisense transcript causes pseudohypoparathyroidism type Ib and biparental defects of GNAS methylation in cis.

ABSTRACT:

Context

GNAS encodes the alpha-subunit of the stimulatory G protein as well as additional imprinted transcripts including the maternally expressed NESP55 and the paternally expressed XLalphas, antisense, and A/B transcripts. Most patients with pseudohypoparathyroidism type Ib (PHP-Ib) exhibit imprinting defects affecting the maternal GNAS allele, which are thought to reduce/abolish Gsalpha expression in renal proximal tubules and thereby cause resistance to PTH.

Objective

Our objective was to define the genetic defect in a previously unreported family with autosomal dominant PHP-Ib.

Design and setting

Analyses of serum and urine chemistries and of genomic DNA and lymphoblastoid-derived RNA were conducted at a tertiary hospital and research laboratory.

Patients

SUBMITTER: Chillambhi S 

PROVIDER: S-EPMC2913043 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature