Cardiac sodium channel mutation in atrial fibrillation.
BACKGROUND
Mutations in the sodium channel SCN5A have been implicated in many cardiac disorders, including the long QT syndrome, Brugada syndrome, conduction system disease, and dilated cardiomyopathy with atrial arrhythmias.


OBJECTIVE
In view of the pleiotropic effects of SCN5A mutations, the purpose of this study was to examine a cohort of patients with familial atrial fibrillation (AF) for mutations in the SCN5A gene.


METHODS
Probands with AF were enrolled in the study between June 1, 2001 and February 10, 2004. Each patient underwent a standardized evaluation, which included an interview, physical examination, ECG, echocardiogram, and blood sample for genetic analysis. Direct sequencing of the coding region of SCN5A was used to screen for mutations in genomic DNA.


RESULTS
One hundred eighty-nine patients with AF were enrolled during the study period. From this cohort, a subset of 57 probands with a family history of AF in at least one first-degree relative was studied. Forty-seven subjects were men (82%); 45 had paroxysmal AF (79%). Echocardiography revealed ejection fraction 62% +/- 6.4 % and left atrial dimension 40 +/- 6.9 mm. A single mutation (N1986K) was observed in one family but was not present in more than 600 control chromosomes. Expression of the N1986K mutant in Xenopus oocytes revealed a hyperpolarizing shift in channel steady-state inactivation.


CONCLUSIONS
In a cohort with familial AF, a single SCN5A mutation causing the arrhythmia in one kindred was identified. These data extend the range of phenotypes observed with SCN5A mutations and suggest that variation in the SCN5A gene is not a major cause of familial AF.
Ellinor
Patrick T
PT
Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. pellinor@partners.org
Nam
Edwin G
EG
Shea
Marisa A
MA
Milan
David J
DJ
Ruskin
Jeremy N
JN
MacRae
Calum A
CA
D001281:Atrial Fibrillation / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006325:Heart Atria / Q000033:anatomy & histology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation; D009206:Myocardium; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010865:Pilot Projects; D015222:Sodium Channels / Q000235:genetics*; D013318:Stroke Volume; D014463:Ultrasonography
D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels