Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency

被引:44
作者
Orii, KE
Aoyama, T
Wakui, K
Fukushima, Y
Miyajima, H
Yamaguchi, S
Orii, T
Kondo, N
Hashimoto, T
机构
[1] GIFU UNIV, SCH MED, DEPT PEDIAT, GIFU 500, JAPAN
[2] SHINSHU UNIV, SCH MED, DEPT BIOCHEM, MATSUMOTO, NAGANO 390, JAPAN
[3] SHINSHU UNIV, SCH MED, DEPT HYG & MED GENET, MATSUMOTO, NAGANO 390, JAPAN
[4] HAMAMATSU UNIV SCH MED, DEPT MED 1, HAMAMATSU, SHIZUOKA 43131, JAPAN
[5] SHIMANE MED UNIV, DEPT PEDIAT, IZUMO, SHIMANE 693, JAPAN
[6] CHUBU GAKUIN UNIV, DEPT HUMAN WELF, GIFU 50132, JAPAN
关键词
D O I
10.1093/hmg/6.8.1215
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mitochondrial trifunctional protein (TP), an enzyme of beta-oxidation, is a multienzyme complex composed of four molecules of the alpha-subunit (HADHA) containing the enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase domains and four molecules of the beta-subunit (HADHB) containing the 3-ketoacyl-CoA thiolase domain. An inborn error of this enzyme complex can cause sudden infant death syndrome, acute hepatic encephalopathy or liver failure, skeletal myopathy, or hypertrophic cardiomyopathy. TP deficiency is classified into two different biochemical phenotypes: one represents the existence of both subunits and the lack of only the 3-hydroxyacyl-CoA dehydrogenase activity and the other represents the absence of both subunits and the lack of all three TP activities, although their clinical features are similar. We have identified two Japanese patients with this disorder. Three enzyme activities of TP were undetectable in fibroblasts from these two patients. We detected two mutations in the HADHB gene from two Japanese patients, an exonic single T insertion which created a new cryptic 5' splice site and a G1331A transition (R411K). Patient 1 was a compound heterozygote, while patient 2 was a homozygote of a G1331A transition.
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页码:1215 / 1224
页数:10
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