Novel SCN5A p.V1429M Variant Segregation in a Family with Brugada Syndrome

International Journal of Molecular Sciences

Michelle M. Monasky¹  Emanuela T. Locati¹  Giuseppe Ciconte¹  Gabriele Vicedomini¹  Emanuele Micaglio¹  Valeria Borrelli¹  Luigi Giannelli¹  Carlo Pappone¹  Giorgio Casari²  Sara Benedetti²  Chiara Di Resta²  Andrea Ghiroldi³  Luigi Anastasia³ 

[1] Arrhythmology Department, IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy;Clinical Genomics—SMEL, IRCCS San Raffaele Hospital, 20132 Milan, 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;    variant;    SCN5A;   

DOI  :  10.3390/ijms21165902

来源: DOAJ

【 摘 要 】

Brugada syndrome (BrS) is diagnosed by the presence of an elevated ST-segment and can result in sudden cardiac death. The most commonly found mutated gene is SCN5A, which some argue is the only gene that has been definitively confirmed to cause BrS, while the potential causative effect of other genes is still under debate. While the issue of BrS genetics is currently a hot topic, current knowledge is not able to result in molecular confirmation of over half of BrS cases. Therefore, it is difficult to develop research models with wide potential. Instead, the clinical genetics first need to be better understood. In this study, we provide crucial human data on the novel heterozygous variant NM_198056.2:c.4285G>A (p.Val1429Met) in the SCN5A gene, and demonstrate its segregation with BrS, suggesting a pathogenic effect. These results provide the first disease association with this variant and are crucial clinical data to communicate to basic scientists, who could perform functional studies to better understand the molecular effects of this clinically-relevant variant in BrS.

【 授权许可】

Unknown