罕见基因突变致Ⅰ型自身免疫性多内分泌腺病综合征1例临床及家系分析

摘要

Objective To analyze the clinical and autoimmune regulator(AIRE)gene mutation characteristics of one case with autoimmune polyendocrinopathy syndrome typeⅠ(APSⅠ)and to further understand APSⅠ.Methods One case of 9-year old male APSⅠ patient was analyzed.Clinical data of the patient was collected and 2 ml venous blood of the patient and his parents as well as his elder brother were extracted.All the exons and adj acent introns of 3 3 immuno-related genes were sequenced by next generation sequencing.AIRE gene mutation was detected and verified by sanger sequencing.Both his parents and elder brother's AIRE gene were analyzed.Results The APSⅠ child patient had repeated oral candidiasis since soon after birth. Tetany and mucocutaneous hyperpigmentation successively appeared at 8 years old.His blood biochemistry and iPTH,ACTH,COR results along with his symptoms accorded with all the three aspects of the APSⅠdiagnostic criteria.AIRE gene test showed compound heterozygous mutation (IVS1 1+1 G>A and AIRE gene heterozygous deletion)for the boy and a heterozygous mutation of IVS1 1+1 G>A for his father respectively. Verification by real-time quantitative polymerase chain reaction (Q-PCR ) showed a heterozygous deletion of AIRE gene for his mother.There was no AIRE gene mutation detected for his elder brother. Conclusion Glands involvement in APSⅠpatients always appeared successively leading to easy misdiagnosis and missed diagnosis.Therefore,more concerons put on new glands involvement during every follow-up.IVS11+1G>A mutation of AIRE gene is rare and its combination with heterozygous deletion of AIRE gene has not been reported.%目的：分析1例Ⅰ型自身免疫性多内分泌腺病综合征(APSⅠ)患儿临床及其家系自身免疫调节因子(autoimmune regulator,AIRE)基因突变特点,以提高对此病认识及诊治水平。方法分析 APSⅠ患儿1例(男性,9岁)。收集该患儿临床资料,并采集患儿及其父母、哥哥静脉血2 ml,采用二代测序技术对患儿33个免疫相关基因的外显子及其相邻内含子进行检测,对所检出的AIRE基因突变采用sanger测序验证,并对患儿父母及其哥哥进行突变分析。结果该 APSⅠ患儿自生后不久即出现反复口腔白色念珠菌感染,8岁先后出现手足搐搦及皮肤黏膜色素沉着,结合血液生化及甲状旁腺激素(iPTH)、促肾上腺皮质激素(ACTH)、皮质醇(COR)检查符合 APSⅠ诊断全部3条标准。AIRE基因检测结果显示患儿为 IVS11+1 G>A 及 AIRE 基因缺失复合杂合突变,患儿父亲为 IVS11+1 G>A杂合突变,实时定量聚合酶链反应(Q-PCR)验证母亲AIRE基因杂合缺失,哥哥未检测到AIRE基因突变。结论APSⅠ患儿多腺体受累常先后相继出现,易误诊及漏诊,随访中应注意有无新受累器官及系统出现；AIRE 基因IVS11+1 G>A突变临床极为罕见,与杂合缺失两者复合杂合突变所致 APSⅠ为首次报道。