caa a22 4500 397575491 CHVBK 20180308164855.0 cr unu---uuuuu 161202e199612 xx s 000 0 eng 10.1093/hmg/5.12.1925 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.12.1925 Identification of Two Mutations in a Compound Heterozygous Child with Dihydrolipoamide Dehydrogenase Deficiency [Elektronische Daten] [Young Soo Hong, Douglas S. Kerr, William J. Craigen, Jie Tan, Yanzhen Pan, Marilyn Lusk, Mulchand S. Patel] An infant girl with elevated blood lactate, pyruvate, and plasma branched-chain amino acids was diagnosed with dihydrolipoamide dehydrogenase (E3; dihydrolipoamide:NAD+ oxidoreductase, EC 1.8.1.4) deficiency. Actvities of the pyruvate dehydrogenase complex and E3 from patient were 26 and 2% of controls in blood lymphocytes, and 11 and 14% in cultured skin fibroblasts, respectively. Western blot analysis demonstrated that the amount of E3 protein in fibroblasts from the patient and her father was about half of controls, while Northern blot analysis showed normal amounts of E3 RNA. DNA sequencing of cloned full-length E3 cDNAs from the patient revealed two mutations in separate alleles. One is a single base insertion of an extra adenine in the last codon of the leader peptide sequence (TAC→TAAC) leading to a nonsense mutation which results in the premature termination of the precursor E3 polypeptide (Y35X). The other is a missense mutation due to substitution of guanine for adenine, causing an Arg→Gly substitution at amino acid 460 of the mature protein (R460G) which triggers the loss of E3 activity probably by structural change in the E3 dimer. DNA sequencing of E3 cDNAs from the parents demonstrated that the nonsense mutation was inherited from the father and the missense mutation was inherited from the mother. © 1993 Oxford University Press Hong Young Soo Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA aut Kerr Douglas S. Departments of Biochemistry and Pediatrics and the Center for Inherited Disorders of Energy Metabolism, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA aut Craigen William J. Departments of Molecular and Human Genetics and Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA aut Tan Jie Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA aut Pan Yanzhen Departments of Molecular and Human Genetics and Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA aut Lusk Marilyn Departments of Biochemistry and Pediatrics and the Center for Inherited Disorders of Energy Metabolism, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA aut Patel Mulchand S. Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA aut Human Molecular Genetics Oxford University Press 5/12(1996-12), 1925-1930 0964-6906 5:12<1925 1996 5 hmg https://doi.org/10.1093/hmg/5.12.1925 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.12.1925 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hong Young Soo Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA aut NATIONALLICENCE 700 1- Kerr Douglas S. Departments of Biochemistry and Pediatrics and the Center for Inherited Disorders of Energy Metabolism, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA aut NATIONALLICENCE 700 1- Craigen William J. Departments of Molecular and Human Genetics and Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA aut NATIONALLICENCE 700 1- Tan Jie Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA aut NATIONALLICENCE 700 1- Pan Yanzhen Departments of Molecular and Human Genetics and Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA aut NATIONALLICENCE 700 1- Lusk Marilyn Departments of Biochemistry and Pediatrics and the Center for Inherited Disorders of Energy Metabolism, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA aut NATIONALLICENCE 700 1- Patel Mulchand S. Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/12(1996-12), 1925-1930 0964-6906 5:12<1925 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford