Characterization of Loss-Of-Function Mutations in Atypical Andersen Tawil Syndrome.
Fiche publication
Date publication
janvier 2021
Journal
Frontiers in genetics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FAIVRE Laurence
Tous les auteurs :
Le Tanno P, Folacci M, Revilloud J, Faivre L, Laurent G, Pinson L, Amedro P, Millat G, Janin A, Vivaudou M, Roux-Buisson N, Fauré J
Lien Pubmed
Résumé
Andersen-Tawil Syndrome (ATS) is a rare disease defined by the association of cardiac arrhythmias, periodic paralysis and dysmorphic features, and is caused by loss-of-function mutations. However, when extracardiac symptoms are atypical or absent, the patient can be diagnosed with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), a rare arrhythmia at high risk of sudden death, mostly due to mutations. The identification of variants in CPVT suspicion is very rare but important because beta blockers, the cornerstone of CPVT therapy, could be less efficient. We report here the cases of two patients addressed for CPVT-like phenotypes. Genetic investigations led to the identification of p. Arg82Trp and p. Pro186Gln variants in the gene Functional studies showed that both variants forms of Kir2.1 monomers act as dominant negative and drastically reduced the activity of the tetrameric channel. We characterize here a new pathogenic variant (p.Pro186Gln) of gene and highlight the interest of accurate cardiologic evaluation and of attention to extracardiac signs to distinguish CPVT from atypical ATS, and guide therapeutic decisions. We also confirm that the gene must be investigated during CPVT molecular analysis.
Mots clés
Andersen-Tawil syndrome, KCNJ2 variants, Kir2.1 channel, Pierre Robin sequence, catecholaminergic polymorphic ventricular tachycardia, functionnal characterization
Référence
Front Genet. 2021 ;12:773177