补体因子Ⅰ缺乏患儿1例分子与临床特征研究

Novel splicing mutation in complement factor Ⅰ of a Chinese patient with recurrent complicated meningo-encephalitis

目的探讨1例补体因子Ⅰ(complement factorⅠ,CFⅠ)缺乏患儿CFⅠ基因突变、蛋白表达水平、免疫表型及临床特征。方法对1例临床表现为反复头痛伴发热,脑电图及脑脊液检查异常的疑似无菌性脑膜脑炎患儿行免疫学筛查,免疫相关基因新一代测序及ELISA检测CFⅠ蛋白表达。结果该患儿补体C3水平明显降低,抗体水平及外周血精细免疫分型正常,经基因分析发现CFⅠ基因第5号内含子拼接位点发生纯合772+1G>T突变,患儿父母均为该突变的携带者。ELISA检测示患儿CFⅠ蛋白表达量与正常对照相比明显降低。结论通过临床、免疫学筛查、基因分析及蛋白检测,确诊1例发生CFⅠ基因突变的补体缺乏患儿,为此前未见报道的新发突变。对反复发热伴头痛,脑膜脑炎诊断不明确及C3降低的患儿应考虑补体缺乏并进行补体相关基因分析以最终确诊。

Complement deficiency is a rare kind of primary immunodeficiency diseases. This study was performed to investigate the clinical characteristics, genetic variation of complement factor ICFI gene and the immunological features in one CFI-deficient case of a 6-year old male patient with recurrent complicated meningo-encephalitis. C3 level, antibody levels, absolute and relative numbers of peripheral lymphocyte subsets were detected, while immune-associated gene mutations was evaluated by gene sequencing technology. Data showed observable reduce of C3 level and a homozygous G〉A substitution located in exon 5 splicing site （772＋ 1） resulting in potentially false mRNA, which resulted in very low expression of CFI protein compared with age-matched healthy boys detected by ELISA. Parents of the patient were identified as heterozygous carriers of the same mutation. In conclusion, a novel splicing mutation of CF I gene has identified in a Chinese CFI -deficient patient with decreased expression of CFI protein. Patient with recurrent complicated meningo-encephalitis and decreased C3 level should be suspected as complement deficiency, thus C3 and CFI gene analysis should be performed for final diagnosis.