RESUMO
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>