Unknown

Dataset Information

0

A novel synonymous variant in exon 1 of GNAS gene results in a cryptic splice site and causes pseudohypoparathyroidism type 1A and pseudo-pseudohypoparathyroidism in a French family.


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 |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC4309471 | biostudies-literature
| S-EPMC3729535 | biostudies-literature
| S-EPMC2840867 | biostudies-literature
| S-EPMC7947960 | biostudies-literature
| S-EPMC8048081 | biostudies-literature
| S-EPMC6065144 | biostudies-literature
| S-EPMC2913043 | biostudies-literature
| S-EPMC4367083 | biostudies-literature
| S-EPMC4394476 | biostudies-literature
| S-EPMC7316974 | biostudies-literature