Two cases of autoimmune polyendocrine syndrome type Ⅰ caused by AIRE gene mutation / 中华内分泌代谢杂志

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.

Two cases of autoimmune polyendocrine syndrome typeⅠcaused by AIRE gene mutation / 中华内分泌代谢杂志

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.

Progress of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy / 国际儿科学杂志

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED)is a clinical rare autosomal recessive disorder.The major clinical manifestations are chronic mucocutaneous candadiasis,hypoparathyroidism and Addison disease.The three manifestations usually occur sequentially.The disease is caused by loss of function mutations in the AIRE gene.The onset,diagnosis,development,therapy and follow-up of this disease usually is the pediatric process.If we can early identify,timely diagnose and treat,regularly follow-up,it will improve children prgnosis and the quality of life,and avoid emergency and severe cases.