Gene Mutation Linked to Familial Sinus Bradycardia

Researchers study family with faulty gene coding in the cardiac pacemaker channel

THURSDAY, Jan. 12 (HealthDay News) -- Italian researchers have identified a mutation in a cardiac pacemaker channel gene that is responsible for some cases of familial sinus bradycardia, according to a study published in the Jan. 12 issue of the New England Journal of Medicine.

Raffaella Milanesi, Ph.D., of the University of Milan in Italy, and colleagues screened 52 bradycardia patients for mutations anywhere in the coding region of the pacemaker-channel gene hHCN4. They identified a missense mutation in exon 7, S672R, in one member of an Italian family with asymptomatic sinus bradycardia (heart rate, 43 beats per minute). The researchers then collected and examined DNA from 27 family members.

Fifteen family members had the gene mutation, and their heart rate was a mean of 52.2 beats per minute. The mean heart rate in family members without the mutation was 73 beats per minute. A functional analysis suggested that "mutant channels respond normally to cAMP but are activated at more negative voltages than are wild-type channels," they report.

"These changes, which mimic those of mild vagal stimulation, slow the heart rate by decreasing the inward diastolic current," the authors write. "The mutation reported here may represent a specific case of a broader mechanism for sinus bradycardia based on constitutive inhibition of pacemaker channels," they conclude.

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