title: Genomic organization and mutational analysis of KVLQT1, a gene responsible for familial long QT syndrome.
abstract: To elucidate the role of the KVLQT1 gene in the pathogenesis of long QT syndrome (LQTS), we have established a screening system for detecting KVLQT1 mutations by the polymerase chain reaction-single strand conformation polymorphism technique (PCR-SSCP). We first determined exon/intron boundaries and flanking intronic sequences, and found that the KVLQT1 gene consists of 17 coding exons. Subsequently, we synthesized oligonucleotide primers to cover the coding region and the flanking intronic sequences, and searched for mutations in 31 Japanese LQTS families. When genomic DNA from each proband was examined by PCR-SSCP followed by direct DNA sequencing, mutations were detected in five families; two independent families carried the same mutation and three of the four were novel. Each mutation was present in affected relatives of the respective proband. This work will enable us to search more thoroughly for LQTS mutations associated with KVLQT1, and eventually will help us in finding genotype/phenotype relationships.
authors.affiliation: Human Genome Center, Institute of Medical Science, University of Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Itoh
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: R
authors.initials: R
authors.lastname: Nagai
authors.forename: K
authors.initials: K
authors.lastname: Kikuchi
authors.forename: S
authors.initials: S
authors.lastname: Ogawa
authors.forename: S
authors.initials: S
authors.lastname: Okada
authors.forename: S
authors.initials: S
authors.lastname: Yamagata
authors.forename: K
authors.initials: K
authors.lastname: Yano
authors.forename: Y
authors.initials: Y
authors.lastname: Yazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007564:Japan; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D017422:Sequence Analysis, DNA
chemical_list: D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated