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 - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Bone Reports Année : 2021

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

Résumé

Pseudohypoparathyroidism type 1A (PHP1A) and pseudopseudohypoparathyroidism (PPHP) (Inactivating PTH/PTHrP Signaling Disorders type 2, IPPSD2) are two rare autosomal disorders caused by lossof-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.

Domaines

Génétique
Fichier principal
Vignette du fichier
Apetrei et al 2021 - jbr GNAS synonyme.pdf (489.05 Ko) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

hal-03283891 , version 1 (12-07-2021)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Andreea Apetrei, Arnaud Molin, Nicolas Gruchy, Manon Godin, Claire Bracquemart, et al.. 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. Bone Reports, 2021, 14, pp.101073. ⟨10.1016/j.bonr.2021.101073⟩. ⟨hal-03283891⟩
39 Consultations
35 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More