|Budget Amount *help
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1996: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1995: ¥4,700,000 (Direct Cost: ¥4,700,000)
LDL-RECEPTOR ABNORMALITIES IN FAMILIAL HYPERCHOLESTEROLEMIA.More than 230 different mutations in the LDL receptor gene have been reported in the world. We have collected 20 homozygotes and more than 1,500 heterozygotes of FH.Nine variants of LDL receptor gene have been identified in our laboratory. Four mutants showed large deletions detected by Southern blot analysis, and 5 mutants were point mutations detected by SSCP analysis and direct sequencing of PCR products. These 9 mutants accounted for only 17.5% of FH.FH Tsuruga showed a point mutation in exon 6 (280 Asp-Tyr). FH Kanazawa-2 showed a point mutaiopn of 395 Arg-Trp. FH Morioka shwoed a point mutation from C to T (395 Arg-Trp) in exon 9.FH Nanao showed 23 stop mutant in exon 2.FH Yokote showed a mutation of 718 stop in exon 15.
CHOLESTERYL-ESTER TRANSFER PROTEIN (CETP) DEFICIENCY IN FAMILIAL HYPER-HDL-CHOLESTEROLEMIA.The genomic DNA of patients with CETP deficiency was used as a substrate for amplification of the CETP gene by PC
R.At the 5'splice donor of intron 14 (position+1) there was a G to A change altering the strictly conserved G-T intron splice donor to A-T.We found two novel mutants of CETP gene. One splice donor site mutant is a thymidine insertion in +3 position in intron 14, which will, again, result in splicing defect. Another new mutant is a missense mutation in exon 15, producing change of aspartic acid into glycine. This mutant is also highly frequent, almost 1 in 10. Thus, these two common mutants produce at least 68 CETP heterozygotes in 718 general subjects, and might raise the HDL-cholesterol levels and reduce coronary heart disease in the Japanese.
LCATDEFICIENCY.The proband is 37 male patient, and his CHOL level was 228mg/dl, HDL-C was 34 mg/dl, his LCAT activity was 0%, and the gene analysis showed a point mutant of 30 Ser-Gly.
MICROSOMAL TRANSFER PROTEIN (MTP) GENE MUTATION IN ABETALIPOPROTEINEMIA.The proband was 29 male patient, and his CHOL level was 33mg/dl, TG was 0mg/dl, and HDL-C was 28mg/dl. The gene analysis showed a point mutation in the junction of exon 10 and intron 9 (G to A), which would produce splicing abnormalities and no MTP protein. Less