Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency

摘要: An infant girl with elevated blood lactate, pyruvate, and plasma branched-chain amino acids was diagnosed dihydrolipoamide dehydrogenase (E3; dihydrolipoamide:NAD + oxidoreductase, EC 1.8.1.4) deficiency. Activities of the pyruvate complex E3 from patient were 26 2% controls in lymphocytes, 11 14% cultured skin fibroblasts, respectively. Western blot analysis demonstrated that amount protein fibroblasts her father about half controls, while Northern showed normal amounts RNA. DNA sequencing cloned full-length cDNAs revealed two mutations separate alleles. One is a single base insertion an extra adenine last codon leader peptide sequence (TAC∀ TAAC) leading to nonsense mutation which results premature termination precursor polypeptide (Y35X). The other missense due substitution guanine for adenine, causing Arg∀ Gly at acid 460 mature (R460G) triggers loss activity probably by structural change dimer. parents inherited mother.