The Clinical Analysis And Autoimmune Regulator Gene Mutation Of Autoimmune Polyendocrinopathy Syndrome Type Ⅰ In A Family: A Report Of One Case

Background:Autoimmune polyendocrinopathy syndrom e type Ⅰ(APS Ⅰ)is a rare autosomal recessive disease due to mutations in the autoimmune regulator(AIRE) gene,which encodes a transcription factor that induces the expression of peripheral tissue-specific antigens in medullary epithelial cells.AIRE plays an important role in induction of T-cell tolerance,and the abse nce of the AIRE protein results in a defective negative selection of self-reactive T-cells, which esca pe to the periphery,causing a multiorgan attack.To date, more than 1 17 different mutations of the AIRE gene have been identified, ranging from a single nucleotide change to large deletions, distributed throughout the gene.In our country,there is rare report about the mutation of the AIRE gene.In 2010,Liu CH and her colleges first reported that Han Chinese APS-1 patient had compound he terozygous mutations of A19 T and R257 X.The purpose of this study was to id entify the underlying genetic cause in a family with APS Ⅰ。Methods:1.The clinical data of one patient with autoimmune polyendocrinopathy syndrome type Ⅰ was collected. 2.Peripheral blood samples were collected from family members.The14 exons of AIRE gene. were amplified by Poly merase Chain Reaction and subsequently sequenced. 3.The region of interest was also am plified and sequenced in 50 unrelated healthy controls. 4.The softwares, Polyphen2,SNPs3 Dand SIFT,were used to predict the possible impact of the mutations on the function of the AIRE protein.Results:1.The patient presented Chronic mucocutaneous candidiasis and Hypoparathyroidism within 3 years,and is diagnosed APS Ⅰ. 2.The results of sequencing showed th at the heterozygous mutation c.622G>T(p.G208W) in exon 5 of the AIRE gene wa s detected in the patient and was a novel mutation, which had not been reported in the HGMD database and latest articles. The mutation was not detected in her parents.3.Analysis of genomic DNA from 50 unrel ated healthy controls revealed a normal sequence at this position,indicating that the detected sequence alteration was a mutation but not a polymorphism. 4..The softwares,Polyphen2,SNPs3 Dand SIFT were used to predict the possible impact of the mutation c.622G>T(p.G208W) on the function of the AIRE protein.In Polyphen2,this mutation is predicted to be probably damaging with a score of 1.000(the higher the score(ranging from 0 to 1)is,the much more damaging the mutation is.), and homology analysis found that the area of mutation is highly conservative in many species.In SNPs3 D,the score of the mutation is-2.1 1( positive value:no damaging;negative value :damaging).In SIFT,the score of the mutation is 0.00(the function of the protein m ay be affected when the score is lower than 0.05).The three software predicted the mutation is probably damaging.Conclusions: The novel mutation of c.622G>T(p.G208W) in AIRE gene m ight play an important role in the pathogenesis of this case of autoimmune polyendocrinopathy syndrome type Ⅰ.