中国人遗传性高铁血红蛋白血症NADH-细胞色素b5还原酶基因L72P突变

Leu 72 Pro mutation in the NADHcytochrome b5 reductase gene found in a Chinese hereditary methemoglobinemia patient

目的：鉴定导致中国人遗传性高铁血红蛋白血症（ＲＣＭ）的ＮＡＤＨ－细胞色素ｂ５还原酶（ｂ５Ｒ）基因突变类型，探讨ＲＣＭ发病的分子基础。方法：逆转录－聚合酶链反应产物直接测序和ｃＤＮＡ克隆测序分析先证者的ｂ５Ｒ编码基因；限制性酶切分析其基因组ＤＮＡ。结果：发现一例ＲＣＭ患者ｂ５Ｒ基因第７２密码子存在新的错义突变（ＣＴＣ→ＣＣＣ）。结论：该突变导致ｂ５Ｒ蛋白第７２位亮氨酸被脯氨酸替换（Ｌ７２Ｐ）是该先证者致病的分子基础；进一步证实Ⅰ型ＲＣＭ患者的ｂ５Ｒ基因突变多发生在近５′端部分。

Objective: To characterize the mutation in NADHcytochrome b5 reductase gene in a Chinese hereditary methemoglobinemia patient, and elucidate the molecular basis of the disease. Methods: b5R gene from a propositus was analyzed by sequencing the RTPCR products as well as cDNA clones; and the results were further confirmed by restriction enzyme analysis of the genomic DNA fragments. Results: A novel mutation was found at codon 72 of b5R gene from the propositus. Conclusion: Replacement of Leu with Pro at codon 72 of b5R gene is the molecular basis of the propositus; and the mutant allele located in 5′ part of b5R gene mainly cause hereditary methemoglobinemia type I. 