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Cardiovascular Genetics: A News Round Up

Summary of Recent Articles of Interest

Wolfgang Lieb, MD and Ramachandran S. Vasan, MD

From the Framingham Heart Study, Framingham, Mass.

Correspondence to Ramachandran S. Vasan, MD, Boston University School of Medicine, Framingham Heart Study, 73 Mount Wayte Avenue, Suite 2, Framingham, MA 01702-5803. E-mail vasan@bu.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Mutations in the ANP Coding Gene Are Involved in Familial Atrial Fibrillation

 
1. Hodgson-Zingman DM, Karst ML, Zingman LV, Heublein DM, Darbar D, Herron KJ, Ballew JD, de Andrade M, Burnett JC Jr, Olson TM. Atrial natriuretic peptide frameshift mutation in familial atrial fibrillation. N Engl J Med. 2008;359:158–165. PMID: 18614783.

Study Hypothesis
Community-based cohort studies and familial clustering of the condition suggest a genetic component in the pathophysiology of atrial fibrillation in some patients. It is conceivable that mutations in specific genes cause atrial fibrillation in certain families.

How Was the Hypothesis Tested?
The authors performed a genome-wide linkage analysis and subsequent fine mapping in a family with 11 affected members to identify a chromosomal locus segregating with the condition. Then, candidate genes in the critical region were sequenced and biochemical analyses as well as animal experiments were performed to assess the biological consequences of the detected mutation.

Principal Findings
Linkage analysis and fine mapping revealed a locus on chromosome 1p36-p35 that cosegregates with the condition. Subsequently, the NPPA gene (encoding atrial natriuretic peptide, ANP), located within the critical region, was sequenced and a heterozygous frameshift mutation (c.456 to 457delAA) was identified in all affected family members but was not detectable in nonaffected family members and in 560 controls with normal ECG and echocardiograms. The mutation abolishes the stop codon and extends the reading frame, which results in an extended chimeric protein consisting of the normal 28 amino acids plus an added 12 residues at the carboxy terminus. In carriers of the mutation, plasma concentration of the mutant ANP protein was 5 to 10 times higher than concentration of . . . [Full Text of this Article]