title: A de novo missense mutation of human cardiac Na+ channel exhibiting novel molecular mechanisms of long QT syndrome.
abstract: Mutations in a human cardiac Na+ channel gene (SCN5A) are responsible for chromosome 3-linked congenital long QT syndrome (LQT3). Here we characterized a de novo missense mutation (R1623Q, S4 segment of domain 4) identified in an infant Japanese girl with a severe form of LQT3. When expressed in oocytes, mutant Na+ channels exhibited only minor abnormalities in channel activation, but in contrast to three previously characterized LQT3 mutations, had significantly delayed macroscopic inactivation. Single channel analysis revealed that R1623Q channels have significantly prolonged open times with bursting behavior, suggesting a novel mechanism of pathophysiology in Na+ channel-linked long QT syndrome.
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan. makitan@med.hokudai.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Makita
authors.forename: N
authors.initials: N
authors.lastname: Shirai
authors.forename: M
authors.initials: M
authors.lastname: Nagashima
authors.forename: R
authors.initials: R
authors.lastname: Matsuoka
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: N
authors.initials: N
authors.lastname: Tohse
authors.forename: A
authors.initials: A
authors.lastname: Kitabatake
mesh_terms: D000818:Animals; D001120:Arginine / Q000235:genetics; D004553:Electric Conductivity; D005260:Female; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007223:Infant; D008133:Long QT Syndrome / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D009206:Myocardium / Q000378:metabolism*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D014981:Xenopus
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels; D005973:Glutamine; D001120:Arginine; D012964:Sodium