A single nucleotide substitution that abolishes the initiator methionine codon of the GLDC gene is prevalent among patients with glycine encephalopathy in Jerusalem.
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.
Boneh
Avihu
A
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.
Korman
Stanley H
SH
Department of Clinical Biochemistry, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel.
Sato
Kenichi
K
Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
Kanno
Junko
J
Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
Matsubara
Yoichi
Y
Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
Lerer
Israela
I
Department of Human Genetics, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel.
Ben-Neriah
Ziva
Z
Department of Human Genetics, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel.
Kure
Shigeo
S
Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
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
D018387:Codon, Initiator; D012333:RNA, Messenger; D013912:Threonine; D008715:Methionine; D000594:Amino Acid Oxidoreductases; D050841:Glycine Dehydrogenase (Decarboxylating); D005998:Glycine