Novel homozygous mutations in AIRE leading to APS-1 and potential mechanisms based on bioinformatics analysis
Background: Autoimmune Poly-endocrine Syndrome Type 1 (APS-1), also known as autoimmune poly-endocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a single-gene hereditary disorder usually characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and autoimmune adrenocortical in...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024040684 |
| _version_ | 1827293937917755392 |
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| author | Huiping Wu Yiqi Mo Shiwen Yu Xiaojun Ye Yili Lu Chaoban Wang Xiaoou Shan |
| author_facet | Huiping Wu Yiqi Mo Shiwen Yu Xiaojun Ye Yili Lu Chaoban Wang Xiaoou Shan |
| author_sort | Huiping Wu |
| collection | DOAJ |
| description | Background: Autoimmune Poly-endocrine Syndrome Type 1 (APS-1), also known as autoimmune poly-endocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a single-gene hereditary disorder usually characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and autoimmune adrenocortical insufficiency. This syndrome is very rare in China. Methods: For our reported patient, we employed clinical and laboratory examinations along with genetic identification. For previously reported cases, we summarized findings based on meta-analysis principles. To investigate the AIRE gene's role in disease, we utilized bioinformatics analysis with existing databases and R language processing. Results: Nucleotide sequence analysis revealed two novel homozygous missense mutations (c.74C > G; c.1612C > T) in the patient's AIRE gene, confirming APS-1 diagnosis. The 3D structure of these mutation sites was described for the first time, showing that altered side chains could affect AIRE protein function. We analyzed 16 genetically diagnosed APS-1 Chinese patients, summarized the AIRE genetic spectrum, and found that exons 1, 2, 3, and 5 were most commonly affected. Hypoparathyroidism and adrenal insufficiency were the most common clinical manifestations (56%–93%), followed by hypothyroidism (31.25%), hypogonadism (12.5%), type 2 diabetes (6.25%), and type 1 diabetes (6.25%). Bioinformatics analysis indicated that AIRE mutations cause antigen presentation abnormalities in immune cells, leading to excessive endogenous and reduced exogenous antigen presentation. Conclusions: Our study summarized the clinical features of APS-1 caused by AIRE gene mutations and explored underlying mechanisms. For some patients, the prophylactic use of antimicrobial agents may be beneficial. These findings guide early genetic screening and inform potential research directions for treatment strategies. |
| first_indexed | 2024-04-24T13:48:26Z |
| format | Article |
| id | doaj.art-9c8664f423c540338b1a0a5a778cffe5 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T13:48:26Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-9c8664f423c540338b1a0a5a778cffe52024-04-04T05:06:40ZengElsevierHeliyon2405-84402024-03-01106e28037Novel homozygous mutations in AIRE leading to APS-1 and potential mechanisms based on bioinformatics analysisHuiping Wu0Yiqi Mo1Shiwen Yu2Xiaojun Ye3Yili Lu4Chaoban Wang5Xiaoou Shan6Department of Pediatric Endocrine, Wenzhou Yuying Children's Hospital, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatric Endocrine, Wenzhou Yuying Children's Hospital, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatric Endocrine, Wenzhou Yuying Children's Hospital, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatric Endocrine, Wenzhou Yuying Children's Hospital, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatric Endocrine, Wenzhou Yuying Children's Hospital, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China; Corresponding author.Department of Pediatric Endocrine, Wenzhou Yuying Children's Hospital, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Corresponding author.Background: Autoimmune Poly-endocrine Syndrome Type 1 (APS-1), also known as autoimmune poly-endocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a single-gene hereditary disorder usually characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and autoimmune adrenocortical insufficiency. This syndrome is very rare in China. Methods: For our reported patient, we employed clinical and laboratory examinations along with genetic identification. For previously reported cases, we summarized findings based on meta-analysis principles. To investigate the AIRE gene's role in disease, we utilized bioinformatics analysis with existing databases and R language processing. Results: Nucleotide sequence analysis revealed two novel homozygous missense mutations (c.74C > G; c.1612C > T) in the patient's AIRE gene, confirming APS-1 diagnosis. The 3D structure of these mutation sites was described for the first time, showing that altered side chains could affect AIRE protein function. We analyzed 16 genetically diagnosed APS-1 Chinese patients, summarized the AIRE genetic spectrum, and found that exons 1, 2, 3, and 5 were most commonly affected. Hypoparathyroidism and adrenal insufficiency were the most common clinical manifestations (56%–93%), followed by hypothyroidism (31.25%), hypogonadism (12.5%), type 2 diabetes (6.25%), and type 1 diabetes (6.25%). Bioinformatics analysis indicated that AIRE mutations cause antigen presentation abnormalities in immune cells, leading to excessive endogenous and reduced exogenous antigen presentation. Conclusions: Our study summarized the clinical features of APS-1 caused by AIRE gene mutations and explored underlying mechanisms. For some patients, the prophylactic use of antimicrobial agents may be beneficial. These findings guide early genetic screening and inform potential research directions for treatment strategies.http://www.sciencedirect.com/science/article/pii/S2405844024040684Autoimmune poly-endocrine syndrome type 1AIRE geneAntigen presentationProphylactic use of antimicrobial agents |
| spellingShingle | Huiping Wu Yiqi Mo Shiwen Yu Xiaojun Ye Yili Lu Chaoban Wang Xiaoou Shan Novel homozygous mutations in AIRE leading to APS-1 and potential mechanisms based on bioinformatics analysis Heliyon Autoimmune poly-endocrine syndrome type 1 AIRE gene Antigen presentation Prophylactic use of antimicrobial agents |
| title | Novel homozygous mutations in AIRE leading to APS-1 and potential mechanisms based on bioinformatics analysis |
| title_full | Novel homozygous mutations in AIRE leading to APS-1 and potential mechanisms based on bioinformatics analysis |
| title_fullStr | Novel homozygous mutations in AIRE leading to APS-1 and potential mechanisms based on bioinformatics analysis |
| title_full_unstemmed | Novel homozygous mutations in AIRE leading to APS-1 and potential mechanisms based on bioinformatics analysis |
| title_short | Novel homozygous mutations in AIRE leading to APS-1 and potential mechanisms based on bioinformatics analysis |
| title_sort | novel homozygous mutations in aire leading to aps 1 and potential mechanisms based on bioinformatics analysis |
| topic | Autoimmune poly-endocrine syndrome type 1 AIRE gene Antigen presentation Prophylactic use of antimicrobial agents |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024040684 |
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