A missense mutation (His42Arg) in the T-protein gene from a large Israeli-Arab kindred with nonketotic hyperglycinemia
A missense mutation (His42Arg) in the T-protein gene from a large Israeli-Arab kindred with nonketotic hyperglycinemia
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来自患有非酮症高甘氨酸血症的大型以色列-阿拉伯亲属的 T 蛋白基因中的错义突变 (His42Arg)
DOI：
10.1007/s004390050716
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发表时间：
1998
期刊：
影响因子：
5.3
通讯作者：
K. Narisawa
中科院分区：
文献类型：
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作者：
Shigeo Kure;H. Mandel;M. Rolland;Y. Sakata;T. Shinka;A. Drugan;A. Boneh;K. Tada;Y. Matsubara;K. Narisawa
非酮性高甘氨酸血症（NKH）是由编码甘氨酸裂解多酶系统组分的基因突变引起的。80%以上的患者存在P蛋白编码基因缺陷，其余患者存在T蛋白编码基因缺陷。我们发现了一个与NKH有血缘关系的以色列阿拉伯人。至少有14名儿童受到影响，所有患者均在出生后2天内出现癫痫发作和呼吸衰竭。酶分析显示，T-蛋白活性缺乏的肝脏标本从一个先证者。我们用直接测序法对该家系进行了T蛋白基因编码区和外显子/内含子边界突变的筛查。在外显子2中发现错义突变;这导致在位置42（H42 R）的氨基酸从组氨酸替换为精氨酸。组氨酸42在人、牛、鸡、豌豆和大肠杆菌中是保守的，表明它在催化功能中具有重要作用。对26名家族成员的基因型分析证实，纯合子H42 R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，这对受影响家庭的遗传咨询是必要的。
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 patints 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, andEscherichia 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.
Kure S.：“芬兰非酮症高甘氨酸血症患者常见突变的鉴定。”
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