title: Gene preference in maple syrup urine disease.
abstract: Untreated maple syrup urine disease (MSUD) results in mental and physical disabilities and often leads to neonatal death. Newborn-screening programs, coupled with the use of protein-modified diets, have minimized the severity of this phenotype and allowed affected individuals to develop into productive adults. Although inheritance of MSUD adheres to rules for single-gene traits, mutations in the genes for E1alpha, E1beta, or E2 of the mitochondrial branched-chain alpha-ketoacid dehydrogenase complex can cause the disease. Randomly selected cell lines from 63 individuals with clinically diagnosed MSUD were tested by retroviral complementation of branched-chain alpha-ketoacid dehydrogenase activity to identify the gene locus for mutant alleles. The frequencies of the mutations were 33% for the E1alpha gene, 38% for the E1beta gene, and 19% for the E2 gene. Ten percent of the tested cell lines gave ambiguous results by showing no complementation or restoration of activity with two gene products. These results provide a means to establish a genotype/phenotype relationship in MSUD, with the ultimate goal of unraveling the complexity of this single-gene trait. This represents the largest study to date providing information on the genotype for MSUD.
authors: Graduate Program in Nutrition and Health Sciences, Emory University School of Medicine, Atlanta, GA, 30322, USA.
authors: M M
authors: MM
authors: Nellis
authors: D J
authors: DJ
authors: Danner
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D015153:Blotting, Western; D002460:Cell Line; D005347:Fibroblasts; D005816:Genetic Complementation Test; D005838:Genotype; D006801:Humans; D007658:Ketone Oxidoreductases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008214:Lymphocytes; D008375:Maple Syrup Urine Disease / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D008928:Mitochondria / Q000201:enzymology; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D021122:Protein Subunits
chemical_list: D009097:Multienzyme Complexes; D021122:Protein Subunits; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)