Molecular heterogeneity in deficiency of complement protein C2 type I.
Molecular heterogeneity in deficiency of complement protein C2 type I.
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I 型补体蛋白 C2 缺乏的分子异质性。
DOI：
10.1046/j.1365-2567.1998.00392.x
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发表时间：
1998
期刊：
影响因子：
6.4
通讯作者：
Colten,HR
中科院分区：
文献类型：
--
作者：
Wang,X;Circolo,A;Lokki,ML;Shackelford,PG;Wetsel,RA;Colten,HR
补体蛋白 C2 (C2D) 缺乏是补体系统最常见的遗传缺陷之一，与风湿病和感染易感性增加有关。两种类型的 C2D 已被识别，每种都在特定的主要组织相容性复合体 (MHC) 单倍型的背景下； I 型，缺失、移码和过早终止密码子，导致可检测到的 C2 蛋白合成缺失；II 型，错义突变，导致 C2 蛋白分泌受阻。对患有 C2 缺陷（与 I 型或 II 型 C2D 相关的 MHC 单倍型不同）和反复感染的儿童中的 C2 表达进行分析，揭示了 C2 缺陷患者中额外的分子异质性。在支持正常人 C2 合成和分泌的条件下，儿童的成纤维细胞中没有合成可检测到的 C2 蛋白，并且儿童的 C2 mRNA 减少至正常值的 42%。 RT-PCR 成纤维细胞 mRNA 和基因组 DNA 的核苷酸测序显示，一个等位基因存在 I 型 C2 缺陷（28 个碱基对缺失），而另一个等位基因的外显子 2 存在先前未被识别的两个碱基对缺失。尽管干扰素-γ适当上调了 Bf，并且在该 C2 缺陷患者中，包含 Bf 启动子的侧翼序列正常，但紧密相连的 B 因子基因的表达显着下降（Bf mRNA 为正常值的 25%）。此外，患者血浆中Bf蛋白的浓度正常。
Deficiency of the complement protein C2 (C2D), one of the most common genetic deficiencies of the complement system, is associated with rheumatological disorders and increased susceptibility to infection. Two types of C2D have been recognized, each in the context of specific major histocompatibility complex (MHC) haplotypes; type I, a deletion, frameshift and premature stop codon resulting in absence of detectable C2 protein synthesis, and type II, missense mutations resulting in a block in secretion of C2 proteins. Analysis of C2 expression in a child with C2 deficiency, a MHC haplotype different from those associated with type I or II C2D, and recurrent infections revealed additional molecular heterogeneity among C2 deficient patients. No detectable C2 protein was synthesized in the child’s fibroblasts under conditions supporting C2 synthesis and secretion in normals and the child’s C2 mRNA was reduced to 42% of normal. Nucleotide sequencing of RT‐PCR fibroblast mRNA and genomic DNA revealed a type I C2 deficiency (28 base‐pair deletion) on one allele and a previously unrecognized two base‐pair deletion in exon 2 on the other. Expression of the closely linked factor B gene was markedly decreased (Bf mRNA 25% of normal), though Bf was up‐regulated appropriately by interferon‐γ and the flanking sequence containing the Bf promoter was normal in this C2‐deficient patient. Moreover, the concentration of Bf protein was normal in the patient’s plasma.