Cao Henian, Hegele Robert A
Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, 406-100 Perth Drive, London, ON N6A 5K8, Canada.
J Hum Genet. 2002;47(11):620-2. doi: 10.1007/s100380200095.
Intracellular concentrations of the nucleotide inosine triphosphate (ITP) are regulated by ITP-ase (EC 3.6.1.19), which is encoded by ITPA on chromosome 20p. Subjects with complete deficiency of ITP-ase activity (MIM 147520) have elevated ITP concentrations in erythrocytes, but no obvious clinical abnormalities. Based on biochemical screening, complete ITP-ase deficiency has been postulated to result from homozygosity for a dysfunctional allele, with an estimated frequency of 0.05 in Caucasians. ITP-ase deficiency has not yet been characterized at the molecular genetic level. Sequencing of the genomic DNA from a Caucasian subject with complete ITP-ase deficiency revealed homozygosity for missense mutation 198C>A, which predicted a threonine for proline substitution at codon 32 (P32T), whereas among 125 normal Caucasians, there were no homozygotes for P32T (P = 0.0079). The P32T allele frequency of 0.07 in Caucasians was similar to the estimates derived from earlier biochemical studies. P32T was found to be present at varying frequency in other ethnic groups. Two common synonymous single-nucleotide polymorphisms were also identified. These ITPAmarkers, including P32T, provide tools for further study of association with clinical and biochemical phenotypes.
核苷酸三磷酸肌苷（ITP）的细胞内浓度受ITP酶（EC 3.6.1.19）调节，该酶由位于20号染色体短臂上的ITPA编码。ITP酶活性完全缺乏的受试者（MIM 147520）红细胞中的ITP浓度升高，但无明显临床异常。基于生化筛查，推测完全性ITP酶缺乏是由功能失调等位基因的纯合性导致的，在白种人中估计频率为0.05。ITP酶缺乏在分子遗传学水平上尚未得到表征。对一名完全缺乏ITP酶的白种人受试者的基因组DNA进行测序，发现其存在错义突变198C>A的纯合性，该突变预测在密码子32处脯氨酸被苏氨酸取代（P32T），而在125名正常白种人中，没有P32T的纯合子（P = 0.0079）。白种人中P32T等位基因频率为0.07，与早期生化研究得出的估计值相似。发现P32T在其他种族群体中的频率各不相同。还鉴定出两个常见的同义单核苷酸多态性。这些ITPA标记，包括P32T，为进一步研究与临床和生化表型的关联提供了工具。
