Analysis of ankyrin-B gene mutations in patients with long QT syndrome.
OBJECTIVE
To identify the ankyrin-B gene mutations that cause long QT syndrome (LQTS) and determine the prevalence of such mutations in Japanese patients with LQTS.


METHODS
We conducted a search for ankyrin-B gene mutation in 78 unrelated patients with LQTS (28 males and 50 females, aged 2 to 89 years). With informed consent from all the subjects and/or their parents, genomic DNA was purified from the white blood cells of the patients and amplified using polymerase chain reaction (PCR). Single-strand conformational polymorphism (SSCP) analysis of the amplified DNA was performed to screen for mutations and aberrant SSCP products were isolated and sequenced by dye terminator cycle sequencing method using an automated fluorescent sequencer. PCR and restriction fragment length polymorphism (PCR-RFLP) analysis was carried out to further confirm the missense mutations by comparison with samples from 150 normal healthy individuals.


RESULTS
We identified a T to A transition mutation at position 4,603 in exon 40, resulting in the substitution of arginine for a tryptophan at amino acid residue 1,535 (W1535R) in the regulatory domain of 220-kD ankyrin-B, which is a highly conserved domain shared by different species.


CONCLUSIONS
This novel missense mutation in the ankyrin-B gene may be a cause of type 4 LQTS. Ankyrin-B gene mutation might not play the major role in LQTS in Japanese.
Zhou
Xiang
X
Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China. zhouslm93@yahoo.com.cn
Shimizu
Masami
M
Konno
Tetsuo
T
Ino
Hidekazu
H
Fujino
Noboru
N
Uchiyama
Katsuharu
K
Mabuchi
Tomohito
T
Kaneda
Tomoya
T
Fujita
Takashi
T
Masuda
Ei-ichi
E
Kato
Hiromasa
H
Funada
Akira
A
Mabuchi
Hiroshi
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D017487:Ankyrins / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017354:Point Mutation
C498994:ANK2 protein, human; D017487:Ankyrins