Kure S, Mandel H, Rolland M O, Sakata Y, Shinka T, Drugan A, Boneh A, Tada K, Matsubara Y, Narisawa K
Department of Biochemical Genetics, Tohoku University School of Medicine, Sendai, Japan.
Hum Genet. 1998 Apr;102(4):430-4. doi: 10.1007/s004390050716.
Nonketotic hyperglycinemia (NKH) is caused by a mutation in the genes encoding the components of the glycine cleavage multi-enzyme system. More than 80% of the patients have defects in the gene encoding P-protein, whereas the rest of the patients have defects in the gene encoding T-protein. We have found a large Israeli-Arab kindred with NKH. At least 14 children were affected, and all the patients had seizures and respiratory failure within 2 days after birth. Enzymatic analysis revealed that T-protein activity was deficient in the liver specimen from one propositus. We screened this family for a mutation in the protein-coding region and exon/intron boundaries of T-protein gene by direct sequencing analysis. A missense mutation was found in exon 2; this resulted in an amino acid substitution from histidine to arginine at position 42 (H42R). Histidine 42 is conserved in human, bovine, chicken, pea, and Escherichia coli, suggesting that it has an important role in catalytic functions. Genotype analyses of 26 family members confirmed that the homozygous H42R mutation was completely associated with the onset of NKH. The availability of DNA testing facilitates the prenatal diagnosis of NKH and the identification of carriers, which is necessary for genetic counseling in the affected families.
非酮症高甘氨酸血症（NKH）是由编码甘氨酸裂解多酶系统各组分的基因突变引起的。超过80%的患者存在编码P蛋白的基因缺陷，其余患者存在编码T蛋白的基因缺陷。我们发现了一个患NKH的大型以色列 - 阿拉伯家族。至少14名儿童患病，所有患者在出生后2天内出现癫痫发作和呼吸衰竭。酶分析显示，一名先证者肝脏标本中的T蛋白活性缺乏。我们通过直接测序分析对该家族的T蛋白基因编码区及外显子/内含子边界进行了突变筛查。在外显子2中发现了一个错义突变；这导致第42位氨基酸由组氨酸替换为精氨酸（H42R）。组氨酸42在人类、牛、鸡、豌豆和大肠杆菌中保守，表明它在催化功能中起重要作用。对26名家族成员的基因型分析证实，纯合H42R突变与NKH的发病完全相关。DNA检测的可用性有助于NKH的产前诊断和携带者的识别，这对于受影响家庭的遗传咨询是必要的。
