title: A single nucleotide substitution that abolishes the initiator methionine codon of the GLDC gene is prevalent among patients with glycine encephalopathy in Jerusalem.
abstract: Glycine encephalopathy (GE) (non-ketotic hyperglycinemia) is an autosomal recessive neurometabolic disease caused by defective activity of the glycine cleavage system. Clinically, patients present usually in the neonatal period with hypotonia, encephalopathy, hiccups and breath arrests with or without overt seizures. GE is considered rare, but its incidence is relatively high in several geographical areas around the world. We report a novel mutation causing GE in six extended Arab families, all from a small suburban village (population 5,000). A methionine to threonine change in the initiation codon of the glycine decarboxylase gene led to markedly reduced glycine decarboxylase mRNA levels and abolished glycine cleavage system activity.
authors.affiliation: Department of Human Genetics, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel. avihu.boneh@ghsv.org.au.|Metabolic Service, Genetic Health Services Victoria, The Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Melbourne, Victoria, 3052, Australia. avihu.boneh@ghsv.org.au.
authors.forename: Avihu
authors.initials: A
authors.lastname: Boneh
authors.affiliation: Department of Clinical Biochemistry, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel.
authors.forename: Stanley H
authors.initials: SH
authors.lastname: Korman
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Kanno
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
authors.affiliation: Department of Human Genetics, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel.
authors.forename: Israela
authors.initials: I
authors.lastname: Lerer
authors.affiliation: Department of Human Genetics, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel.
authors.forename: Ziva
authors.initials: Z
authors.lastname: Ben-Neriah
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000235:genetics*; D019943:Amino Acid Substitution; D018912:Arabs / Q000235:genetics*; D018387:Codon, Initiator / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005998:Glycine / Q000378:metabolism*; D050841:Glycine Dehydrogenase (Decarboxylating); D006801:Humans; D020158:Hyperglycinemia, Nonketotic / Q000201:enzymology / Q000235:genetics*; D007557:Israel; D008297:Male; D008715:Methionine / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013912:Threonine / Q000737:chemistry / Q000235:genetics
chemical_list: D018387:Codon, Initiator; D012333:RNA, Messenger; D013912:Threonine; D008715:Methionine; D000594:Amino Acid Oxidoreductases; D050841:Glycine Dehydrogenase (Decarboxylating); D005998:Glycine