Abstract:

Autosomal recessive（AR） and X-linked recessive （XR） primary immunodeficiencies（PIDs） are mainly caused by alleles with some loss-of-function（LOF）. Alleles with LOF can lead to defects of mRNA or protein expressions. The autosomal dominant（AD） PIDs can be caused by LOF alleles，What’s more， the AD disorders can be also due to gene mutations of gain-of-function（GOF），Most heterozygous GOF alleles can lead to enhancement of gene function or abnormal activation of expression products，resulting in related clinical symptoms. Up to 18 AD PIDs have been described with a wide range of immunological and clinical forms. Auto-inflammation and auto-immunity are  found to be most common. Other clinical manifestations include infections，allergies or malignancies.

Key words: immunodeficiency, gene mutation, gain-of-function mutation, loss-of-function mutation

摘要：

以常染色体隐性遗传（AR）和X-连锁隐性遗传 （XR）方式起病的原发性免疫缺陷病（PID） 多表现为功能丧失性突变（LOF），LOF造成相关免疫基因不表达或表达不足、表达产物功能完全丧失或明显降低进而引发PID。而以常染色体显性遗传（AD）方式起病的PID除可表现为LOF外，还可表现为功能获得性突变（GOF），GOF可造成相关免疫基因功能增强或异常活化，进而引起相关临床表现。目前已发现18种PID由GOF基因突变所致，其临床表型复杂，免疫学异质性明显，常以自身炎症或自身免疫为主要表现，伴或不伴其他经典PID的临床特征如反复感染、过敏、肿瘤等。

关键词: 免疫缺陷, 基因突变, 功能获得性突变, 功能丧失性突变