title: Concomitant Brugada-like and short QT electrocardiogram linked to SCN5A mutation.
abstract: Mutations in the α-subunit of cardiac sodium channel gene SCN5A can lead to the overlapping phenotypes of both the Brugada and type 3 long QT syndromes. However, the combination of Brugada and a short QT phenotype resulting from mutation in SCN5A has not previously been described. A man with concomitant Brugada-like and short QT electrocardiogram (ECG) was identified and the SCN5A gene was sequenced. Whole-cell patch clamp analysis of human embryo kidney (HEK) 293 cells expressing a SCN5A channel with the patient's sequence was used to investigate the biophysical properties of the channel. The patient with the family history of sudden death showed Brugada-like and short QT interval ECG. Sequence analysis of the coding region of the SCN5A gene, identified a G to A heterozygous missense mutation at nucleotide site 2066 that resulted in a amino-acid substitution of arginine to histidine at amino-acid site 689 (R689H). Patch clamp analysis showed that the R689H failed to generate current when heterologously expressed in HEK293 cells, indicating it was a loss-of-function mutation. Our finding firstly shows that a heterozygous missense mutation R689H in SCN5A gene results in the loss of protein function and the coexistents of the Brugada-like and short QT interval ECG phenotypes.
authors.affiliation: Cardiology Department, The Second Affiliated Hospital of Nanchang University, Nanchang, China. hongkui88@163.com
authors.forename: Kui
authors.initials: K
authors.lastname: Hong
authors.forename: Jinzhu
authors.initials: J
authors.lastname: Hu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
mesh_terms: D000200:Action Potentials; D000328:Adult; D001120:Arginine / Q000235:genetics; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000235:genetics*; D053840:Brugada Syndrome / Q000235:genetics; D004562:Electrocardiography; D057809:HEK293 Cells; D006579:Heterozygote; D006639:Histidine / Q000235:genetics; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics* / Q000502:physiology
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D006639:Histidine; D001120:Arginine