Novel SCN5A p.W697X Nonsense Mutation Segregation in a Family with Brugada Syndrome

International Journal of Molecular Sciences

Giuseppe Ciconte¹  EmanuelaT. Locati¹  Gabriele Vicedomini¹  Emanuele Micaglio¹  MichelleM. Monasky¹  Valeria Borrelli¹  Luigi Gianelli¹  Carlo Pappone¹  Chiara Di Resta²  Maurizio Ferrari³  Sara Benedetti³  Rosanna Bagnulo⁴  Nicoletta Resta⁴  Andrea Ghiroldi⁵  Luigi Anastasia⁵ 

[1] Arrhythmology Department, IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy;Genomic Unit for the Diagnosis of Human Pathologies, Division of Genetics and Cellular Biology, IRCCS San Raffaele Hospital, 20132 Milan, Italy;Laboratory of Clinical Molecular Biology and Cytogenetics, Division of Genetics and Cellular Biology, IRCCS San Raffaele Hospital, 20132 Milan, Italy;Medical Genetics Unit, Department of Biomedical Sciences and Human Oncology, “Aldo Moro” University of Bari, Policlinico Hospital, 70121 Bari, Italy;Stem Cells for Tissue Engineering Laboratory, IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy;

关键词: brugada syndrome;    sudden cardiac death;    genetic testing;    mutation;    scn5a;    sodium channel;    arrhythmia;    channelopathy;    family;    point-nonsense mutation;   

DOI  :  10.3390/ijms20194920

来源: DOAJ

【 摘 要 】

Brugada syndrome (BrS) is marked by an elevated ST-segment elevation and increased risk of sudden cardiac death. Variants in the SCN5A gene are considered to be molecular confirmation of the syndrome in about one third of cases, while the genetics remain a mystery in about half of the cases, with the remaining cases being attributed to variants in any of a number of genes. Before research models can be developed, it is imperative to understand the genetics in patients. Even data from humans is complicated, since variants in the most common gene in BrS, SCN5A, are associated with a number of pathologies, or could even be considered benign, depending on the variant. Here, we provide crucial human data on a novel NM_198056.2:c.2091G>A (p.Trp697X) point-nonsense heterozygous variant in the SCN5A gene, as well as its segregation with BrS. The results herein suggest a pathogenic effect of this variant. These results could be used as a stepping stone for functional studies to better understand the molecular effects of this variant in BrS.

【 授权许可】

Unknown