Ontology highlight
ABSTRACT: Introduction
Pseudohypoparathyroidism type 1A (PHP1A) and pseudopseudohypoparathyroidism (PPHP) (Inactivating PTH/PTHrP Signaling Disorders type 2, IPPSD2) are two rare autosomal disorders caused by loss-of-function mutations on either maternal or paternal allele, respectively, in the imprinted GNAS gene, which encodes the α subunit of the ubiquitously-expressed stimulatory G protein (Gαs).Case presentation
We investigated a synonymous GNAS variant NM_001077488.2: c.108C>A / p.(Val36=) identified in a family presenting with IPPSD2 phenotype. In silico splicing prediction algorithms were in favor of a deleterious effect of this variant, by creating a new donor splicing site. The GNAS expression studies in blood suggested haploinsufficiency and showed an alternate splice product demonstrating the unmasking of a cryptic site, leading to a 34 base pairs deletion and the creation of a probable unstable RNA.We present the first familial case of IPPSD2 caused by a pathogenic synonymous variant in GNAS gene.
SUBMITTER: Apetrei A
PROVIDER: S-EPMC8100090 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
Apetrei Andreea A Molin Arnaud A Gruchy Nicolas N Godin Manon M Bracquemart Claire C Resbeut Antoine A Rey Gaëlle G Nadeau Gwenaël G Richard Nicolas N
Bone reports 20210423
<h4>Introduction</h4>Pseudohypoparathyroidism type 1A (PHP1A) and pseudopseudohypoparathyroidism (PPHP) (Inactivating PTH/PTHrP Signaling Disorders type 2, IPPSD2) are two rare autosomal disorders caused by loss-of-function mutations on either maternal or paternal allele, respectively, in the imprinted <i>GNAS</i> gene, which encodes the α subunit of the ubiquitously-expressed stimulatory G protein (Gαs).<h4>Case presentation</h4>We investigated a synonymous <i>GNAS</i> variant NM_001077488.2: c ...[more]