Identification of the mutations in the T-protein gene causing typical and atypical nonketotic hyperglycinemia

Springer Science and Business Media LLC - Tập 93 - Trang 655-658 - 1994
Kenji Nanao1, Kazuko Okamura-Ikeda2, Yutaro Motokawa2, David M. Danks3, E. Regula Baumgartner4, Goro Takada1, Kiyoshi Hayasaka1,5
1Department of Pediatrics, Akita University School of Medicine, Akita, Japan
2Institute for Enzyme Research, University of Tokushima, Tokushima, Japan
3Murdoch Institute, Royal Children's Hospital, Parkville, Australia
4Metabolic Unit, University Children’s Hospital, Basel, Switzerland
5Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan

Tóm tắt

We have investigated the molecular lesions of T-protein deficiency causing typical or atypical nonketotic hyperglycinemia (NKH) in two unrelated pedigrees. A patient with typical NKH was identified as being homozygous for a missense mutation in the T-protein gene, a G-to-A transition leading to a Gly-to-Asp substitution at amino acid 269 (G269D). Sibling patients of a second family with atypical NKH had two different missense mutations in the T-protein gene (compound heterozygote), a G-to-A transition leading to a Gly-to-Arg substitution at amino acid 47 (G47R) in one allele, and a G-to-A transition leading to an Arg-to-His substitution at amino acid 320 (R320H) in the other allele. Gly 269 is conserved in T-proteins of various species, even in E. coli, whereas Gly 47 and Arg 320 are replaced by Ala and Leu, respectively, in E. coli. The mutation occurring in more conservative amino acid residues thus results in more deleterious damage to the T-protein, and gives the severe clinical phenotype, viz., typical NKH.

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