title: Identification of a common mutation in Finnish patients with nonketotic hyperglycinemia.
abstract: Nonketotic hyperglycinemia (NKH) is an autosomal recessive metabolic disorder caused by the defects in the glycine cleavage system (GCS; EC 2.1.2.10), a multienzyme system that consists of four individual components. NKH is a rare disorder in many countries, but with a very high incidence in northern Finland. To understand the genetic background of this high incidence, we examined the GCS in a typical case of NKH at the molecular level. The activity of P protein, a component of the GCS, was not detected in the lymphoblasts of the patient, while P protein mRNA of a normal size and level was present in the cells. Structural analysis of P protein mRNA from the patient revealed a single nucleotide substitution from G to T in the protein coding region, which resulted in an amino acid alteration from Ser564 to Ile564. No P protein activity was detected when the mutant P protein with this amino acid substitution was expressed in COS 7 cells. The patient was homozygous for this mutation. Furthermore, this mutation was present in 70% (14 of 20) of P protein gene alleles in Finnish patients with NKH, whereas it was not found in 20 alleles of non-Finnish patients. The results suggest that this mutation is responsible for the high incidence of NKH in Finland.
authors.affiliation: Department of Biochemical Genetics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kure
authors.forename: M
authors.initials: M
authors.lastname: Takayanagi
authors.forename: K
authors.initials: K
authors.lastname: Narisawa
authors.forename: K
authors.initials: K
authors.lastname: Tada
authors.forename: J
authors.initials: J
authors.lastname: Leisti
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000453:epidemiology / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D005387:Finland / Q000453:epidemiology; D005838:Genotype; D005998:Glycine / Q000097:blood*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D015995:Prevalence
chemical_list: D005998:Glycine