2024-03-29T15:04:54Z
https://tsukuba.repo.nii.ac.jp/oai
oai:tsukuba.repo.nii.ac.jp:00017625
2024-01-25T07:45:31Z
2780:761
3:62:5592:675
Heterogeneous mutations in the human lipoprotein lipase gene in patients with familial lipoprotein lipase deficiency
Gotoda, T
山田, 信博
ヤマダ, ノブヒロ
YAMADA, Nobuhiro
Kawamura, M
Kozaki, K
Mori, N
Ishibashi, S
Shimano, H
Takaku, F
Yazaki, Y
Furuichi, Y
Murase, T
The DNA sequences were determined for the lipoprotein lipase (LPL) gene from five unrelated Japanese patients with familial LPL deficiency. The results demonstrated that all five patients are homozygotes for distinct point mutations dispersed throughout the LPL gene. Patient 1 has a G-to-A transition at the first nucleotide of intron 2, which abolishes normal splicing. Patient 2 has a nonsense mutation in exon 3 (Tyr61----Stop) and patient 3 in exon 8 (Trp382----Stop). The latter mutation emphasizes the importance of the carboxy-terminal portion of the enzyme in the expression of LPL activity. Missense mutations were identified in patient 4 (Asp204----Glu) and patient 5 (Arg243----His) in the strictly conserved amino acids. Expression study of both mutant genes in COS-1 cells produced inactive enzymes, establishing the functional significance of the two mis-sense mutations. In these patients, postheparin plasma LPL mass was either virtually absent (patients 1 and 2) or significantly decreased (patients 3-5). To detect these mutations more easily, we developed a rapid diagnostic test for each mutation. We also determined the DNA haplotypes for patients and confirmed the occurrence of multiple mutations on the chromosomes with an identical haplotype. These results demonstrate that familial LPL deficiency is a heterogeneous genetic disease caused by a wide variety of gene mutations.
journal article
The American Society for Clinical Investigation
1991-12
application/pdf
The journal of clinical investigation
6
88
1856
1864
0021-9738
AA00695520
https://tsukuba.repo.nii.ac.jp/record/17625/files/JCI_88-6.pdf
eng
1752947
https://doi.org/10.1172/JCI115507
© The American Society for Clinical Investigation
open access