title: A novel mutation in FKBP12.6 binding region of the human cardiac ryanodine receptor gene (R2401H) in a Japanese patient with catecholaminergic polymorphic ventricular tachycardia.
abstract: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an autosomal dominant inherited disorder characterized by adrenergic induced polymorphic ventricular tachycardias and associated with sudden cardiac death. The human cardiac ryanodine receptor gene (RyR2) was linked to CPVT. A 20-year-old male was referred to our hospital because of recurrent syncope after physical and emotional stress. Routine cardiac examinations including catheterization revealed no structural abnormality. Exercise on treadmill induced premature ventricular contraction in bigeminy and bidirectional ventricular tachycardia was induced during isoproterenol infusion. Beta-blocking drug was effective in suppressing the arrhythmias. We performed genetic screening by PCR-SSCP method followed by DNA sequencing, and a novel missense mutation R2401H in RyR2 located in FKBP12.6 binding region was identified. This mutation was not detected in 190 healthy controls. Since FKBP12.6 plays a critical role in Ca channel gating, the R2401H mutation can be expected to alter Ca-induced Ca release and E-C coupling resulting in CPVT. This is the first report of RyR2 mutation in CPVT patient from Asia including Japan.
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Aizawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ueda
authors.forename: Satoru
authors.initials: S
authors.lastname: Komura
authors.forename: Takashi
authors.initials: T
authors.lastname: Washizuka
authors.forename: Masaomi
authors.initials: M
authors.lastname: Chinushi
authors.forename: Natsuko
authors.initials: N
authors.lastname: Inagaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Takeharu
authors.initials: T
authors.lastname: Hayashi
authors.forename: Megumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Noritsugu
authors.initials: N
authors.lastname: Nakano
authors.forename: Michio
authors.initials: M
authors.lastname: Yasunami
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
authors.forename: Masayasu
authors.initials: M
authors.lastname: Hiraoka
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000318:Adrenergic beta-Agonists / Q000009:adverse effects*; D000328:Adult; D005080:Exercise Test / Q000009:adverse effects / Q000379:methods; D006801:Humans; D007545:Isoproterenol / Q000009:adverse effects*; D008297:Male; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D019837:Ryanodine Receptor Calcium Release Channel / Q000097:blood / Q000235:genetics*; D017180:Tachycardia, Ventricular / Q000097:blood / Q000139:chemically induced / Q000235:genetics*; D022021:Tacrolimus Binding Proteins / Q000235:genetics*
chemical_list: D000318:Adrenergic beta-Agonists; D019837:Ryanodine Receptor Calcium Release Channel; D022021:Tacrolimus Binding Proteins; C403484:tacrolimus binding protein 1B; D007545:Isoproterenol