Life-threatening infectious diseases of childhood: single-gene inborn errors of immunity?
Life-threatening infectious diseases of childhood: single-gene inborn errors of immunity?
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DOI：
10.1111/j.1749-6632.2010.05834.x
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Casanova, Jean-Laurent
中科院分区：
文献类型：
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作者：
Alcais, Alexandre;Quintana-Murci, Lluis;Casanova, Jean-Laurent
传染病背后的先天免疫缺陷假说正在获得实验支持。然而，在不同的疾病和不同的研究中，易感性或抗性的明显遗传模式差异很大。缺乏传染病的连贯遗传结构。我们认为，儿童时期发生在原发性感染过程中的危及生命的传染病，主要是由个别罕见的、但总体上多样的、临床外显率可变的单基因变异引起的，而成人继发性或再激活性感染易感性的遗传成分则更为复杂。这一模式符合：(1)幼儿期大多数传染病的高发病率，然后稳步下降；㈡单基因或多基因易感性对育龄前传染病发病率分布的影响的理论建模；（三）现有的儿童和成人传染病单基因和复杂遗传学的分子证据；（四）目前对原发性和继发性或潜伏性感染免疫的认识；（五）儿童和成人非传染性疾病临床遗传学的最新状况；（六）单基因和复杂疾病风险基因的进化数据。随着新一代深度重测序的出现，这种潜在的严重儿科传染病的单基因变异模型在实验上是可测试的。
The hypothesis that inborn errors of immunity underlie infectious diseases is gaining experimental support. However, the apparent modes of inheritance of predisposition or resistance differ considerably among diseases and among studies. A coherent genetic architecture of infectious diseases is lacking. We suggest here that life-threatening infectious diseases in childhood, occurring in the course of primary infection, result mostly from individually rare but collectively diverse single-gene variations of variable clinical penetrance, whereas the genetic component of predisposition to secondary or reactivation infections in adults is more complex. This model is consistent with (i) the high incidence of most infectious diseases in early childhood, followed by a steady decline; (ii) theoretical modeling of the impact of monogenic or polygenic predisposition on the incidence distribution of infectious diseases before reproductive age; (iii) available molecular evidence from both monogenic and complex genetics of infectious diseases in children and adults; (iv) current knowledge of immunity to primary and secondary or latent infections; (v) the state of the art in the clinical genetics of noninfectious pediatric and adult diseases; and (vi) evolutionary data for the genes underlying single-gene and complex disease risk. With the recent advent of new-generation deep resequencing, this model of single-gene variations underlying severe pediatric infectious diseases is experimentally testable.