1990 Fiscal Year Final Research Report Summary
Molecular Genetics of Familial Hyperlipidemias
| Project/Area Number |
63480187
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | Kanazawa University |
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Principal Investigator |
MABUCHI Hiroshi University of Kanazawa Department of Medicine Associate Professor, 医学部, 助教授 (00019960)
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| Project Period (FY) |
1988 – 1990
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| Keywords | Familial hypercholesterolenia (FH) / LDL-receptor / FH-Tonami-1 / FH-Tonami-2 / Apo B-100 gene abnormality / Homozygous familial hyper-HDL-emia / CETP gene abnormality |
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| Research Abstract |
Results are follows ;
1) LDL-receptor (LDL-R) gene abnormalities in familial hypercholesterolemia (FH)
LDL-R gene analysis of heterozygous FH patients from 210 families revealed four new mutants. (1) FH-Tonami-1 : This LDL-R gene mutant showed a partial deletion of about 6kb including exon 15 and its neighboring introns. In the normal cultured skin fibroblasts, about 120KD of LDL-R precursor protein proceeded into a mature 160KD, while in this mutant cells the smaller precursors of 100KD never proceeded into mature forms and were destroyed in the cells. (2) FH-Tonami-2 : This mutant shows a deletion of about 10kb including exons 2 and 3, and produces a partial deficiency of bind-binding domain of the receptor. The activity of the mutant receptor is about 40% of normal, and therefore, this mutant produces a mild type of FH, and the four homozygous patients of this mutant survive to reach the ages of 64, 53, 51, 35 years. (3) FH-Kanazawa and FH-Okayama are proved to be new mutants of LDL-R
2) Two patients from a family showed the familial defective apolipoprotein B-100, showing one point mutation of exon 26, changing amino acid 3500 (Arg) into Gln.
3) Cholesteryl ester transfer protein (CETP) deficiency Homozygous familial hyper-HDL-emia has proved to be produced by a deficiency of CETP, and the deficiency of the CETP gene has been proved to be a G to A mutation of the junction of exon 14 and intron 14. Ten homozygous and 20 heterozygous patients with CETP deficiency were discovered in Japan, and the deficiency of CETP has been found to produce a hypo-LDL-emia as well hyper-HDL-emia.
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