TY - JOUR
T1 - Molecular defect in familial lecithin:Cholesterol acyltransferase (LCAT) deficiency
T2 - A single nucleotide insertion in LCAT gene causes a complete deficient type of the disease
AU - Bujo, Hideaki
AU - Kusunoki, Jun
AU - Ogasawara, Masahito
AU - Yamamoto, Tokuo
AU - Ohta, Yoshiaki
AU - Shimada, Toshisune
AU - Saito, Yasushi
AU - Yoshida, Sho
N1 - Funding Information:
We thank Dr. Kohji Shii (Toho University, Tokyo) for help and encouragement.T his investigation was supportedi n part by researchg rantsf rom the Ministry of Education, Sciencea nd Culture(No. 01570351),a nd from the Ministry of Health and Welfare, Japan.
PY - 1991/12/31
Y1 - 1991/12/31
N2 - Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a hereditary disorder with clinical manifestations including corneal opacity, premature atherosclerosis and renal failure. In this study, we analyzed the molecular base underlying a case of Japanese LCAT deficiency, in which both LCAT mass and activity of the proband were nearly absent. DNA blot hybridization analysis showed no gross rearrangement in the LCAT gene of the proband. The nucleotide sequence analysis of the cloned LCAT gene demonstrated only an extra nucleotide "C" insertion at the first exon, when compared to the sequence of wild type. This single base insertion caused a shift of the following reading frame, probably resulting in a truncated abnormal LCAT polypeptide that consist of only 16 amino acids. The direct sequence analysis of PCR-amplified DNA showed only the same insertion, indicating that the LCAT-deficient proband is a homozygote for the mutant allele. These results indicate that the clinical and biochemical feature of the patient is mainly caused by a complete deficiency of the enzyme based on a homozygous abnormality of LCAT gene.
AB - Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a hereditary disorder with clinical manifestations including corneal opacity, premature atherosclerosis and renal failure. In this study, we analyzed the molecular base underlying a case of Japanese LCAT deficiency, in which both LCAT mass and activity of the proband were nearly absent. DNA blot hybridization analysis showed no gross rearrangement in the LCAT gene of the proband. The nucleotide sequence analysis of the cloned LCAT gene demonstrated only an extra nucleotide "C" insertion at the first exon, when compared to the sequence of wild type. This single base insertion caused a shift of the following reading frame, probably resulting in a truncated abnormal LCAT polypeptide that consist of only 16 amino acids. The direct sequence analysis of PCR-amplified DNA showed only the same insertion, indicating that the LCAT-deficient proband is a homozygote for the mutant allele. These results indicate that the clinical and biochemical feature of the patient is mainly caused by a complete deficiency of the enzyme based on a homozygous abnormality of LCAT gene.
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U2 - 10.1016/0006-291X(91)92026-G
DO - 10.1016/0006-291X(91)92026-G
M3 - Article
C2 - 1662503
AN - SCOPUS:0026315409
VL - 181
SP - 933
EP - 940
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -