GNAS AS2 methylation status enables mechanism-based categorization of pseudohypoparathyroidism type 1B.

ABSTRACT: Pseudohypoparathyroidism type 1B (PHP1B) results from aberrant genomic imprinting at the GNAS gene. Defining the underlying genetic cause in new patients is challenging because various genetic alterations (e.g., deletions, insertions) within the GNAS genomic region, including the neighboring STX16 gene, can cause PHP1B, and the genotype-epigenotype correlation has not been clearly established. Here, by analyzing patients with PHP1B with a wide variety of genotypes and epigenotypes, we identified a GNAS differentially methylated region (DMR) of distinct diagnostic value. This region, GNAS AS2, was hypomethylated in patients with genetic alterations located centromeric but not telomeric of this DMR. The AS2 methylation status was captured by a single probe of the methylation-sensitive multip

SUBMITTER: Iwasaki Y 

PROVIDER: S-EPMC10972583 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature