Sodium channel gene (SCN5A) mutations in 44 index patients with Brugada syndrome: Different incidences in familial and sporadic disease

Abstract

The Brugada syndrome (BS) is a distinct form of idiopathic ventricular fibrillation and may cause sudden cardiac death in healthy young individuals. In the surface ECG, BS can be recognized by an atypical right bundle branch block and ST-segment elevation in the right precordial leads. Mutations in the cardiac sodium channel gene SCN5A are only known to cause BS. In a multi-center effort, we have collected clinical data on 44 unrelated index patients and family members and performed a complete genetic analysis of SCN5A. In 37% the disease was familial, whereas in the majority it was sporadic (63%). Five novel SCN5A mutations (2602delC, resulting in: E867X; 2581_2582del TT: F861fs951X; 2673G>A: E1225K; 4435_4437delAAG: K1479del; and 5425C>A: S1812X) were found and were randomly located in SCN5A. Mutation frequencies (SCN5A+) differed significantly between familial (38%) and sporadic disease (0%) (p=0.001). Disease penetrance was complete in the SCN5A+ adult patients, but incomplete in SCN5A+ children (17%). Genetic testing of SCN5A is especially useful in familial disease to identify individuals at cardiac risk. In sporadic cases, however, a genetic basis and the value of mutation screening has to be further determined. These results are in line with a possibly genetic and clinical heterogeneity of BS.

Novel SCN5A mutation (Q55X) associated with age-dependent expression of Brugada syndrome presenting as neurally mediated syncope

“…The age-dependent manifestation of Brugada syndrome correlates well with previous observations that the ECG penetrance in the mutation carriers of Brugada syndrome is considerably lower in children than adults (17% vs. 100%, respectively) 14 . Furthermore, in a large family with overlapping phenotypes of Brugada syndrome and long QT syndrome due to an SCN5A mutation 1795insD, QT prolongation was recognized from birth onward, whereas ST elevation became apparent only after 5 years 15 .…”

Ventricular tachycardia in a Brugada syndrome patient caused by a novel deletion in SCN5A

“…Hence, the results suggest that the patient suffered from haploinsufficiency of Na v 1.5, and that this mutation was the cause of his Brugada syndrome. 2 . L'analyse de mutation du gène SCN5A a révélé une nouvelle mutation, une mutation à trame décalée T de la délétion 3480, entraînant une troncation prématurée de la protéine.…”

“…In a series of eight cases, they showed that ST elevation in leads V 1 to V 3 in patients with a structurally normal heart was associated with an inherited form of sudden cardiac death. Mutations in the gene encoding the pore-forming sodium channel SCN5A, giving rise to the Na v 1.5 protein, have been shown to cause 15% to 20% of Brugada syndrome cases (2)(3)(4). The pattern of inheritance is autosomal dominant, and the penetrance of the disease is not 100%.…”

Brugada syndrome and cardiac sodium channelopathy overlap syndromes: different faces of SCN5A mutations

“…Однако, учитывая, что тахикардия типа «пируэт» никог-да не была задокументирована, продление Q-T можно было бы клинически связать с комбина-цией терапии амиодароном и тяжестью дефек-тов проводимости, которые могут вызвать удли-нение интервала Q-T. Генотипирование выяви-ло в 20-м экзоне гена SCN5A новую нуклеотидную замену c.3650T>G, приводящую к замене неполярного, гидрофобного лейцина (L) положительно заряженным, гидрофильным аргинином (R) в положении 1217 (L1217R) обла-сти DIII-S1. Для расположенных рядом мутаций (S1219N и E1225K), влияющих на DIII белка NaV1.5, показана связь с синдромом Бругада [20,25]. [26] и указана в международном сборнике му-таций SCN5A для синдрома Бругада [20].…”