RESUMEN
Objective@#To analyze the mutation of autoimmune regulator ( AIRE ) gene in a pedigree with autoimmune polyendocrine syndrome type Ⅰ (APS-Ⅰ). @*Methods@#The peripheral blood samples from family members were collected for DNA extraction, and then the mutation sites on AIRE gene were screened by PCR and Sanger sequencing. The mutation sites were further verified in 100 healthy persons by the created restriction site PCR (CRS-PCR) and PCR restriction fragment length polymorphism (PCR-RFLP). The effects of mutation on the structure and function of AIRE protein were analyzed with SIFT, PolyPhen-2, Mutation Taster and Antheprot Editor softwares. The effects of mutation on the splicing sites of AIRE mRNA were predicted with Alternative Splice Site Predictor, FruitFly Splice Predictor and SplicePort softwares, and further verified by Sanger sequencing. @*Results@#Two novel heterozygous mutations c.47 C＞G T16R and c.1631-2 A＞T were found in the proband. The c.47 site is highly conserved and homologous in different species. The missense mutation of c.47C＞G changed the secondary structure and hydrophobicity of AIRE protein, and affected its function. The c.1631 -2 A＞T mutation changed the splicing site of AIRE mRNA, and led to the deletion of exon 13. @*Conclusion@#Two novel pathogenic mutations c.47 C＞G T16R and c.1631-2 A＞T are identified in a pedigree with autoimmune polyendocrine syndrome type Ⅰ.