Complete deficiency of the sixth complement component (C6Q0), susceptibility to Neisseria meningitidis infections and analysis of the frequencies of C6Q0 gene defects in South Africans
Complete deficiency of the sixth complement component (C6Q0), susceptibility to Neisseria meningitidis infections and analysis of the frequencies of C6Q0 gene defects in South Africans
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DOI：
10.1111/j.1365-2249.2011.04525.x
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发表时间：
2012-03
影响因子：
4.6
通讯作者：
A. Orren;E. Owen;H. Henderson;L. van der Merwe;F. Leisegang;C. Stassen;P. Potter
中科院分区：
文献类型：
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作者：
A. Orren;E. Owen;H. Henderson;L. van der Merwe;F. Leisegang;C. Stassen;P. Potter
完全补体成分 6 缺乏症 (C6Q0) 是一种共同显性遗传病，表现为对侵袭性脑膜炎奈瑟菌感染的易感性增加。受影响的个体有两个受影响的等位基因，它们可以是纯合的，也可以是复合杂合的，因为它们携带的特定基因缺陷。这种疾病在南非西开普省的诊断相对频繁。受影响的患者接受青霉素预防治疗。 2004 年，我们开始了对 46 名患者的临床随访研究。其中，43 人有家庭年龄匹配的 C6 充分对照。参与者被分类为 (i) 健康，或 (ii) 患有严重疾病 (SI) 或死亡 (D)。 SI 是一种无法进行正常日常活动的长期疾病。在 43 名患者中，21 名健康，22 名 SI/D；而在 43 名匹配对照者中，35 名健康，8 名 SI/D。这种差异非常显着。在所有 46 名 C6Q0 患者中，反复感染的患者的 SI/D 明显高于未感染或仅感染过一次的患者。因此，这项工作证明了脑膜炎球菌病（MD）反复发作的长期严重后果。我们调查了 2250 名新生儿中已知影响 Cape 患者的四种 C6Q0 致病性突变（828delG、1138delC、821delA 和 1879delG）的频率。总共检测到 103 个缺陷等位基因 (2·28%) 和 3 个受影响的 C6Q0 个体。对于所有缺陷的总和，预计 10 000 名个体中有 5·24 名受影响受试者 (C6Q0)。目前尚不清楚有多少 C6Q0 个体患有 MD 或其他传染病。
Complete complement component 6 deficiency (C6Q0) is a co‐dominant genetic disease presenting as increased susceptibility to invasive Neisseria meningitidis infections. Affected individuals have two affected alleles which can be homozygous or compound heterozygous for the particular gene defects they carry. This disorder has been diagnosed relatively frequently in Western Cape South Africans. Affected patients are prescribed penicillin prophylaxis. In 2004 we commenced a clinical follow‐up study of 46 patients. Of these, 43 had family age‐matched C6 sufficient controls. Participants were classified as either (i) well, or (ii) having a serious illness (SI) or died (D). An SI was a long‐term illness that did not allow the performance of normal daily activities. Among 43 patients, 21 were well and 22 were SI/D, while among 43 matched controls, 35 were well and eight were SI/D. This difference is highly significant. Among all 46 C6Q0 patients, those who had had recurrent infection had significantly more SI/D than those who had suffered none or one infection. Thus, this work demonstrates the long‐term serious outcome of repeated meningococcal disease (MD) episodes. We investigated the frequencies of four C6Q0 pathogenic mutations known to affect Cape patients (828delG, 1138delC, 821delA and 1879delG) in 2250 newborns. A total of 103 defective alleles (2·28%) and three affected C6Q0 individuals were detected. For all defects combined, 5·24 affected subjects (C6Q0) are expected among 10 000 individuals. What is still unknown is the number of C6Q0 individuals who suffer MD or other infectious diseases.