The first confirmed case with C3 deficiency caused by compound heterozygous mutations in the C3 gene;: a new aspect of pathogenesis for C3 deficiency
The first confirmed case with C3 deficiency caused by compound heterozygous mutations in the C3 gene;: a new aspect of pathogenesis for C3 deficiency
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DOI：
10.1016/j.bcmd.2007.11.002
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发表时间：
2008-05-01
影响因子：
2.3
通讯作者：
Ariga, Tadashi
中科院分区：
文献类型：
--
作者：
Kida, Miyuki;Fujioka, Hirotaka;Ariga, Tadashi
补体系统是一种古老的级联系统，在先天性和适应性免疫中起主要作用。组分C3是三种补体途径的中心。遗传性补体3（0）缺乏症的特点是严重的复发性感染和免疫复合物紊乱是极其罕见的疾病。自1972年以来，遗传性C3缺乏症已被描述在许多家庭代表各种民族起源;然而，只有8个家庭的这些案件已确定其遗传缺陷。有趣的是，除了一个（不完整的分析），所有被证明具有纯合C3基因突变。以前我们提出了一个假设，基于C3合成的独特过程; C3缺乏症不是作为一个简单的常染色体隐性遗传性状遗传的。在这里，我们报告了第一例确诊的C3缺乏症引起的复合杂合突变。这两个突变分别是：第24外显子的一个碱基插入（3176 insT），该插入可导致第26外显子的移码和下游提前终止密码子（K1105 X）;第26外显子的一个无义突变C3303 G（Y1081 X），该突变以前被报道为纯合突变。这一证实的病例表明，我们提出的假设有一个新的方面的发病机制的C3缺乏症的前景。(C)2007爱思唯尔公司All rights reserved.
The complement system is an ancient cascade system that has a major role in innate and adaptive immunity. Component C3 is central to the three complement pathways. Hereditary compliment 3 (0) deficiency characterized by severe recurrent infections and immune complex disorders is extremely rare disease. Since 1972, inherited C3 deficiency has been described in many families representing a variety of national origins; however, only 8 families of these cases have been identified their genetic defects. Interestingly, all except one (incomplete analysis) were shown to harbor homozygous C3 gene mutations. Previously we proposed a hypothesis, based on the unique process of C3 synthesis; C3 deficiency is not inherited as a simple autosomal recessive trait. Here, we report the first confirmed case with C3 deficiency caused by compound heterozygous mutations. They were a novel one base insertion (3176insT) in exon 24 which is predicted to result in a frameshift and a premature downstream stop codon (K1105X) in exon 26, and a nonsense mutation of C3303G (Y1081X) in exon 26 which was previously reported as homozygous mutations. This confirmed case suggests that our proposed hypothesis has prospects of a new aspect of pathogenesis for C3 deficiency. (C) 2007 Elsevier Inc. All rights reserved.