Abstract
Mitochondrial trifunctional protein (MTP) deficiency is a rare inherited metabolic disorder of mitochondrial fatty acid oxidation. We newly characterized three novel mutations in 2 Japanese patients with MTP deficiency, and investigated the clinical and molecular aspects of 5 Japanese patients including 3 previously reported cases. Herein, we describe the characterization of four missense mutations, R214C, H346R, R411K, and V422G, in the HADHB gene, which have been identified in Japanese patients, employing a newly developed, sensitive transient expression analysis. Co-transfection of wild-type HADHA and HADHB cDNAs in SV40-transfected fibroblasts from a MTP-deficient patient yielded sufficient enzyme activity to evaluate low-level residual enzyme activity, using two incubation temperatures of 30 °C and 37 °C. At 30 °C, residual enzyme activity was higher than that at 37 °C in V422G, R214C, and R411K. However, H346R, which was seen in the most severe case, showed no enzyme activity at both temperatures. Our results demonstrate that a defect of HADHB in MTP deficiency is rather common in Japanese patients, and the mutational spectrum is heterogeneous. The present findings showed that all missense mutations in this study were disease-causing. Although the number of patients is still limited, it is suggested that the phenotype is correlated with the genotype and a combination of two mutant alleles of the HADHB gene in MTP deficiency.
| Original language | English |
|---|---|
| Pages (from-to) | 372-377 |
| Number of pages | 6 |
| Journal | Molecular Genetics and Metabolism |
| Volume | 98 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Dec 1 2009 |
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All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Biochemistry
- Molecular Biology
- Genetics
- Endocrinology
Cite this
Clinical and molecular aspects of Japanese patients with mitochondrial trifunctional protein deficiency. / Purevsuren, Jamiyan; Fukao, Toshiyuki; Hasegawa, Yuki; Kobayashi, Hironori; Li, Hong; Mushimoto, Yuichi; Fukuda, Seiji; Yamaguchi, Seiji.
In: Molecular Genetics and Metabolism, Vol. 98, No. 4, 01.12.2009, p. 372-377.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Clinical and molecular aspects of Japanese patients with mitochondrial trifunctional protein deficiency
AU - Purevsuren, Jamiyan
AU - Fukao, Toshiyuki
AU - Hasegawa, Yuki
AU - Kobayashi, Hironori
AU - Li, Hong
AU - Mushimoto, Yuichi
AU - Fukuda, Seiji
AU - Yamaguchi, Seiji
PY - 2009/12/1
Y1 - 2009/12/1
N2 - Mitochondrial trifunctional protein (MTP) deficiency is a rare inherited metabolic disorder of mitochondrial fatty acid oxidation. We newly characterized three novel mutations in 2 Japanese patients with MTP deficiency, and investigated the clinical and molecular aspects of 5 Japanese patients including 3 previously reported cases. Herein, we describe the characterization of four missense mutations, R214C, H346R, R411K, and V422G, in the HADHB gene, which have been identified in Japanese patients, employing a newly developed, sensitive transient expression analysis. Co-transfection of wild-type HADHA and HADHB cDNAs in SV40-transfected fibroblasts from a MTP-deficient patient yielded sufficient enzyme activity to evaluate low-level residual enzyme activity, using two incubation temperatures of 30 °C and 37 °C. At 30 °C, residual enzyme activity was higher than that at 37 °C in V422G, R214C, and R411K. However, H346R, which was seen in the most severe case, showed no enzyme activity at both temperatures. Our results demonstrate that a defect of HADHB in MTP deficiency is rather common in Japanese patients, and the mutational spectrum is heterogeneous. The present findings showed that all missense mutations in this study were disease-causing. Although the number of patients is still limited, it is suggested that the phenotype is correlated with the genotype and a combination of two mutant alleles of the HADHB gene in MTP deficiency.
AB - Mitochondrial trifunctional protein (MTP) deficiency is a rare inherited metabolic disorder of mitochondrial fatty acid oxidation. We newly characterized three novel mutations in 2 Japanese patients with MTP deficiency, and investigated the clinical and molecular aspects of 5 Japanese patients including 3 previously reported cases. Herein, we describe the characterization of four missense mutations, R214C, H346R, R411K, and V422G, in the HADHB gene, which have been identified in Japanese patients, employing a newly developed, sensitive transient expression analysis. Co-transfection of wild-type HADHA and HADHB cDNAs in SV40-transfected fibroblasts from a MTP-deficient patient yielded sufficient enzyme activity to evaluate low-level residual enzyme activity, using two incubation temperatures of 30 °C and 37 °C. At 30 °C, residual enzyme activity was higher than that at 37 °C in V422G, R214C, and R411K. However, H346R, which was seen in the most severe case, showed no enzyme activity at both temperatures. Our results demonstrate that a defect of HADHB in MTP deficiency is rather common in Japanese patients, and the mutational spectrum is heterogeneous. The present findings showed that all missense mutations in this study were disease-causing. Although the number of patients is still limited, it is suggested that the phenotype is correlated with the genotype and a combination of two mutant alleles of the HADHB gene in MTP deficiency.
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UR - http://www.scopus.com/inward/citedby.url?scp=70350621065&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2009.07.011
DO - 10.1016/j.ymgme.2009.07.011
M3 - Article
C2 - 19699128
AN - SCOPUS:70350621065
VL - 98
SP - 372
EP - 377
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
SN - 1096-7192
IS - 4
ER -