title: Novel missense mutations in the glutamate dehydrogenase gene in the congenital hyperinsulinism-hyperammonemia syndrome.
abstract: OBJECTIVE
  The objectives of this study were to clarify the involvement of the glutamate dehydrogenase gene in congenital hyperinsulinemia-hyperammonemia syndrome (CHHS) and the relationships between the mutation of the gene and clinical severity.
  
  
  METHODS
  Five unrelated Japanese patients (3 girls and 2 boys) with CHHS were investigated. All patients had convulsions or loss of consciousness resulting from hypoglycemia at less than 1 year of age. We examined mutations of the glutamate dehydrogenase gene using genomic or reverse-transcriptase polymerase chain reactions, followed by direct sequencing.
  
  
  RESULTS
  We identified heterozygous missense mutations in all patients. Three patients had a previously identified mutation (C-->T at nt 1506) at codon 445 in the allosteric domain. Two novel missense mutations were identified in the other patients. These mutations included a change of A-->C at nt 1059 and a change of G-->A at nt 966, within the catalytic domain of the glutamate dehydrogenase gene. The locus of the mutations was not associated with the severity of hypoglycemia.
  
  
  CONCLUSIONS
  Our results suggest that structural aberrations of not only the allosteric domain but also the catalytic domain of the glutamate dehydrogenase protein, caused by missense mutations, can result in the development of CHHS.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, the University of Tokyo, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Miki
authors.forename: T
authors.initials: T
authors.lastname: Taki
authors.forename: T
authors.initials: T
authors.lastname: Ohura
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000225:Adenine; D000641:Ammonia / Q000097:blood*; D003062:Codon / Q000235:genetics; D003596:Cytosine; D005260:Female; D005969:Glutamate Dehydrogenase / Q000235:genetics*; D006147:Guanine; D006579:Heterozygote; D006801:Humans; D006946:Hyperinsulinism / Q000151:congenital* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D007003:Hypoglycemia / Q000503:physiopathology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D012640:Seizures / Q000503:physiopathology; D013577:Syndrome; D013941:Thymine; D014474:Unconsciousness / Q000503:physiopathology
chemical_list: D003062:Codon; D006147:Guanine; D000641:Ammonia; D003596:Cytosine; D005969:Glutamate Dehydrogenase; D000225:Adenine; D013941:Thymine