ABSTRACT
Objective@#Autoimmune polyendocrine syndrome type Ⅰ(APS-Ⅰ) is caused by mutations in the autoimmune regulator gene (AIRE) gene. In this study, phenotype and AIRE gene analysis were performed in two patients with APS-Ⅰ.@*Methods@#Peripheral blood samples were collected from two patients with APS-Ⅰ and their families. All exons of the AIRE gene and adjacent exon-intron sequences were amplified by PCR and subsequently sequenced. The silico analysis was performed to predict the possible impact of the mutations on the function of the AIRE protein. At the same time, 100 healthy controls were selected to confirm the mutation.@*Results@#Case 1 was a 31-year-old female who exhibited chronic mucocutaneous candidiasis, hypoparathyroidism, Addison′s disease, Hashimoto′s thyroiditis, and premature ovarian failure. A homozygous c. 483_484insC mutation in exon 4 of AIRE gene was identified in this patient. Her parents, siblings and son were heterozygous for this mutation, which is consistent with the autosomal recessive inheritance pattern. Case 2 was a 34-year-old male who had mucocutaneous candidiasis, Addison′s disease, primary hypoparathyroidism, and Hashimoto′s thyroiditis. A compound heterozygous AIRE mutation (c.179A>G/C.463+ 2T>C) were identified in this patient. His father was heterozygous for c. 179A>G mutation, and his mother was heterozygous for C. 463+ 2T>C, which is consistent with autosomal recessive inheritance mode. The c. 483_484insC and c. 463+ 2T>C have been reported to be pathogenic. The c. 179A>G mutation was predicted pathogenic by SIFT and PolyPhen2 software, which was not detected in 100 healthy controls. It has not been reported in the HGDM database and is a novel mutation.@*Conclusion@#We identified a novel AIRE gene mutation (c.179A>G), which contributed to further understanding of the pathogenesis of APS-Ⅰ. The clinical variation and rarity of APS-Ⅰ makes the syndrome hard to recognize. Early recognition of symptoms and screening for AIRE mutation in patients with APS-Ⅰ has important clinical implications for the diagnosis and treatment.
ABSTRACT
Objective Autoimmune polyendocrine syndrome typeⅠ( APS-Ⅰ) is caused by mutations in the autoimmune regulator gene ( AIRE) gene. In this study, phenotype and AIRE gene analysis were performed in two patients with APS-Ⅰ. Methods Peripheral blood samples were collected from two patients with APS-Ⅰand their families. All exons of the AIRE gene and adjacent exon-intron sequences were amplified by PCR and subsequently sequenced. The silico analysis was performed to predict the possible impact of the mutations on the function of the AIRE protein. At the same time, 100 healthy controls were selected to confirm the mutation. Results Case 1 was a 31-year-old female who exhibited chronic mucocutaneous candidiasis, hypoparathyroidism, Addison' s disease, Hashimoto's thyroiditis, and premature ovarian failure. A homozygous c.483484insC mutation in exon 4 of AIRE gene was identified in this patient. Her parents, siblings and son were heterozygous for this mutation, which is consistent with the autosomal recessive inheritance pattern. Case 2 was a 34-year-old male who had mucocutaneous candidiasis, Addison' s disease, primary hypoparathyroidism, and Hashimoto' s thyroiditis. A compound heterozygous AIRE mutation (c.179A>G/C.463+2T>C) were identified in this patient. His father was heterozygous for c.179A>G mutation, and his mother was heterozygous for C.463+2T>C, which is consistent with autosomal recessive inheritance mode. The c.483484insC and c. 463+2T>C have been reported to be pathogenic. The c. 179A>G mutation was predicted pathogenic by SIFT and PolyPhen2 software, which was not detected in 100 healthy controls. It has not been reported in the HGDM database and is a novel mutation. Conclusion We identified a novel AIRE gene mutation ( c.179A>G) , which contributed to further understanding of the pathogenesis of APS-Ⅰ. The clinical variation and rarity of APS-Ⅰmakes the syndrome hard to recognize. Early recognition of symptoms and screening for AIRE mutation in patients with APS-Ⅰhas important clinical implications for the diagnosis and treatment.
ABSTRACT
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.