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).
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.
Bardien-Kruger
Soraya
S
University of Stellenbosch/Medical Research Council Centre for Molecular and Cellular Biology, Department of Medical Physiology and Biochemistry, University of Stellenbosch Medical School, Tygerberg, South Africa.
Wulff
Heike
H
Arieff
Zainu
Z
Brink
Paul
P
Chandy
K George
KG
Corfield
Valerie
V
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D003001:Cloning, Molecular; D004247:DNA; D006327:Heart Block / Q000235:genetics*; D006331:Heart Diseases / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D051637:Shaker Superfamily of Potassium Channels; D018911:Trinucleotide Repeats
C431140:KCNA7 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051637:Shaker Superfamily of Potassium Channels; D004247:DNA