Intragenic Deletions of GNAS in Pseudohypoparathyroidism Type 1A Identify a New Region Affecting Methylation of Exon A/B.

ABSTRACT: Pseudohypoparathyroidism type 1A (PHP1A) and pseudopseudohypoparathyroidism (PPHP) are caused by inactivating mutations in the exons of GNAS that encode the alpha-subunit of the stimulatory G protein (Gsα). In some cases abnormal methylation of exon A/B of GNAS, a hallmark of PHP1B, has been reported. To identify the underlying genetic basis for PHP1A/PPHP in patients in whom molecular defects were not detected by GNAS sequencing and microarray-based analysis of copy number variations. Whole genome sequencing (WGS) and pyrosequencing of differentially methylated regions (DMRs) of GNAS using genomic deoxyribonucleic acid from affected patients. We identified 2 novel heterozygous GNAS deletions: a 6.4 kb deletion that includes exon 2 of GNAS in the first proband that was associated with norm

SUBMITTER: Li D 

PROVIDER: S-EPMC7947960 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature