Objectives 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 bea cause of type 4LQTS. Ankyrin-B gene mutation might not play the major role in LQTS in Japanese.

BACKGROUND: CETP(Cholesteryl ester transfer Protein) is the essential protein for 'reverse cholesterol transport' which transfers cholesteryl ester from HDL particles to other lipoproteins. The subjects with CETP deficiency caused by genetic mutation in the CETP gene have very high HDL levels that CETP deficiency implies anti-atherogenic effect. A missense mutation in the exon 15(D442G) and a splicing defect in the intron 14(Int 14A) in the CETP gene are reported to be popular among Japanese population which overall prevalence of both mutations is up to 10%. METHODS: To identify the CETP mutaion such as D442G or Int 14A among Koreans, seven subjects who have high HDL level above 80mg/dl and 14 first-degree relatives of them were included in this study. RESULTS: Of 21 subjects in 7 familes, 5 subjects in 2 families were confirmed as D442G mutation of CETP gene, but Int 14A mutation is not found. Subjects with D442G mutation have high apo A-I levels as well as HDL levels. CONCLUSION: The D442G mutation of CETP gene is firstly confirmed in Koreans. The CETP deficiency caused by genetic mutation in the CETP gene seems to be prevalent among Korean population.
Apolipoprotein A-I ; Asian Continental Ancestry Group ; Cholesterol ; Exons ; Humans ; Introns ; Korea ; Lipoproteins ; Mutation, Missense ; Prevalence