Identification of a common mutation in Finnish patients with nonketotic hyperglycinemia

S. Kure, M. Takayanagi, K. Narisawa, K. Tada, J. Leisti

研究成果: Article査読

63 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)160-164
ページ数5
ジャーナルJournal of Clinical Investigation
90
1
DOI
出版ステータスPublished - 1992

ASJC Scopus subject areas

  • Medicine(all)

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