Characterisation of the human voltage-gated potassium channel gene, KCNA7, a candidate gene for inherited cardiac disorders, and its exclusion as cause of progressive familial heart block I (PFHBI).

Abstract

Mutations in genes encoding cardiac ion channels and their subunits are responsible for several genetic cardiac disorders. We characterised the human gene KCNA7, encoding the voltage-gated potassium channel Kv1.7 and compared its coding sequence with that of the mouse orthologue, kcna7. Both genes are encoded by two exons separated by a conserved intron, unlike all the other Kv1-family genes that contain intronless coding regions. KCNA7 and kcna7 encode proteins of 456 amino acid residues that share >95% sequence identity, and the mouse channel has biophysical and pharmacological properties closely resembling the ultra-rapidly activating delayed rectifier (I(Kur)) in cardiac tissue. Using reverse transcriptase-PCR, KCNA7 mRNA was detected in adult human heart. We determined that KCNA7 resides on chromosome 19q13.3 in a region that also contains the progressive familial heart block I (PFHBI) locus. Direct sequencing of KCNA7's coding sequence in PFHB1-affected individuals revealed no pathogenic sequence changes, but two single nucleotide polymorphisms detected in exon 2 result in amino acid substitutions. These results provide evidence for the exclusion of this candidate as the PFHB1-causative gene, although mutations in regulatory and non-coding regions cannot be excluded. As ion channel-encoding genes have been implicated in a growing number of genetic conditions, the data presented may facilitate further analysis of the role of KCNA7 and its product in the heart.

• Authors: Soraya Bardien-Kruger, Heike Wulff, Zainu Arieff, Paul Brink, K George Chandy, Valerie Corfield
• Journal: European journal of human genetics : EJHG (Eur J Hum Genet) Vol. 10 Issue 1 Pg. 36-43 (Jan 2002) ISSN: 1018-4813 [Print] England
• PMID: 11896454 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• KCNA7 protein, human
• Potassium Channels
• Potassium Channels, Voltage-Gated
• Shaker Superfamily of Potassium Channels
• DNA

Topics

• Amino Acid Sequence
• Animals
• Base Sequence
• COS Cells
• Cloning, Molecular
• DNA
• Heart Block (genetics)
• Heart Diseases (genetics)
• Humans
• Mice
• Molecular Sequence Data
• Potassium Channels (genetics, physiology)
• Potassium Channels, Voltage-Gated
• Shaker Superfamily of Potassium Channels
• Trinucleotide Repeats