کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1998846 1065821 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Clinical and molecular aspects of Japanese patients with mitochondrial trifunctional protein deficiency
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Clinical and molecular aspects of Japanese patients with mitochondrial trifunctional protein deficiency
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 98, Issue 4, December 2009, Pages 372–377
نویسندگان
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