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)

Soraya Bardien-Kruger, Heike Wulff, Zainu Arieff, Paul Brink, K. George Chandy, Valerie Corfield

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 ultrarapidly activating delayed rectifier (IKur) 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.

Original languageEnglish (US)
Pages (from-to)36-43
Number of pages8
JournalEuropean Journal of Human Genetics
Volume10
Issue number1
DOIs
StatePublished - Jan 1 2002

Fingerprint

Voltage-Gated Potassium Channels
Genes
Ion Channels
Exons
Mutation
Inborn Genetic Diseases
Amino Acid Substitution
Reverse Transcriptase Polymerase Chain Reaction
Introns
Single Nucleotide Polymorphism
Hereditary bundle branch system defect
Chromosomes
Pharmacology
Amino Acids
Messenger RNA
Proteins

Keywords

  • Inherited cardiac conduction disorders
  • KCNA7
  • kcna7
  • Kv1.7
  • l
  • PFHB1
  • Potassium channels

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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). / Bardien-Kruger, Soraya; Wulff, Heike; Arieff, Zainu; Brink, Paul; Chandy, K. George; Corfield, Valerie.

In: European Journal of Human Genetics, Vol. 10, No. 1, 01.01.2002, p. 36-43.

Research output: Contribution to journalArticle

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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 ultrarapidly activating delayed rectifier (IKur) 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.",
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