Nanao K, Okamura-Ikeda K, Motokawa Y, Danks D M, Baumgartner E R, Takada G, Hayasaka K
Department of Pediatrics, Akita University School of Medicine, Japan.
Hum Genet. 1994 Jun;93(6):655-8. doi: 10.1007/BF00201565.
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.
我们研究了两个不相关家系中导致典型或非典型非酮症高甘氨酸血症（NKH）的T蛋白缺乏的分子病变。一名典型NKH患者被鉴定为T蛋白基因错义突变的纯合子，即G到A的转变导致第269位氨基酸由甘氨酸变为天冬氨酸（G269D）。第二个患有非典型NKH的家族中的同胞患者在T蛋白基因中有两个不同的错义突变（复合杂合子），一个等位基因中G到A的转变导致第47位氨基酸由甘氨酸变为精氨酸（G47R），另一个等位基因中G到A的转变导致第320位氨基酸由精氨酸变为组氨酸（R320H）。甘氨酸269在各种物种的T蛋白中都是保守的，甚至在大肠杆菌中也是如此，而甘氨酸47和精氨酸320在大肠杆菌中分别被丙氨酸和亮氨酸取代。因此，发生在更保守氨基酸残基上的突变对T蛋白造成的损害更大，并导致严重的临床表型，即典型NKH。
