Persad Amanda S, Kameoka Yosuke, Kanda Shuji, Niho Yoshiyuki, Suzuki Kazuo
Department of Bioactive Molecules, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Gene Expr. 2006;13(2):67-71. doi: 10.3727/000000006783991863.
Animal models suggest that a deficiency in myeloperoxidase (MPO; EC 1.11.1.7), a lysosomal hemoprotein involved in host defense, may be associated with a decreased level of immunity. A nonsynonymous mutation, resulting in an arginine to cysteine substitution (Arg499Cys or R499C), has been identified in the exon 9 genetic coding region of a Japanese patient with complete MPO deficiency. Genetic analysis revealed that the mRNA of the patient could be correctly transcribed then further translated into a peptide sequence. However, the Western blot analysis confirmed the absence of MPO peptides. An initial screening assay of the patient's blood exhibited an abnormal hematograph, and no MPO activity was detected. To determine if this mutation might be associated with MPO deficiency, DNA samples for 387 controls were examined. Genetic analysis was performed using standard PCR techniques for amplification and sequencing. None of the control samples possessed the R499C substitution. This mutation is in close proximity to a different mutation (G501S) previously found in another Japanese MPO-deficient patient, and the amino acid, H502, which is strongly involved in heme binding, leading to the speculation that heme binding may play a role in complete MPO deficiency.
动物模型表明，髓过氧化物酶（MPO；EC 1.11.1.7）缺乏可能与免疫力下降有关，MPO是一种参与宿主防御的溶酶体血红蛋白。在一名患有完全性MPO缺乏症的日本患者的第9外显子遗传编码区域中，已鉴定出一种非同义突变，该突变导致精氨酸被半胱氨酸取代（Arg499Cys或R499C）。基因分析显示，该患者的mRNA能够正确转录，然后进一步翻译成肽序列。然而，蛋白质免疫印迹分析证实不存在MPO肽。对该患者血液进行的初步筛查检测显示血细胞计数异常，且未检测到MPO活性。为了确定这种突变是否可能与MPO缺乏有关，对387名对照的DNA样本进行了检测。使用标准PCR技术进行基因分析以进行扩增和测序。对照样本均未出现R499C取代。该突变与先前在另一名日本MPO缺乏症患者中发现的另一种不同突变（G501S）非常接近，并且氨基酸H502强烈参与血红素结合，这导致推测血红素结合可能在完全性MPO缺乏中起作用。
