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This research evaluates three patients with AAI, including autoimmune polyglandular syndrome (APS) type 2. Two patients had APS or AAI during childhood, and one had a history of endocrine autoimmune disease, indicating a possible hereditary basis of the condition. Trio-based exome sequencing and high-resolution HLA typing were employed to analyze patients and their parents. Benign or likely benign variants of the <jats:italic>AIRE<\/jats:italic> gene were identified in all participants of the study. These variants, coupled with clinical data and the results of antibody studies to type I interferons, helped to exclude APS-1. Patients with APS-2, in contrast to patient with AAI, inherited distinct variants of unknown significance in the <jats:italic>CLEC16A<\/jats:italic> gene, which is associated with autoimmune diseases, including AAI. Various risk alleles in other genes associated with autoimmunity were identified in all patients. HLA typing of class II loci revealed alleles related to APS. Nevertheless, the frequencies of the haplotypes identified are substantial in the healthy Russian population. Immunological tests can detect antibody carriers and assess the risk of autoimmune disease development. In the future, to identify genetic predictors of autoimmune endocrinopathies, it is recommended to analyze the whole genome of patients and their relatives, examining clinically relevant variants in non-coding regions.<\/jats:p>","DOI":"10.1371\/journal.pone.0312335","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T17:30:04Z","timestamp":1729272604000},"page":"e0312335","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Trio-based exome sequencing and high-resolution HLA typing in families of patients with autoimmune adrenal insufficiency and autoimmune polyglandular syndrome"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7894-9222","authenticated-orcid":true,"given":"Anastasiia","family":"Buianova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Yukina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery","family":"Cheranev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Suchalko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Shmitko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Samitova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6876-3336","authenticated-orcid":true,"given":"Nurana","family":"Nuralieva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Kulagina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Savvateeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Troshina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Rebrikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3183-318X","authenticated-orcid":true,"given":"Dmitry","family":"Gryadunov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1343-2550","authenticated-orcid":true,"given":"Dmitriy","family":"Korostin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"pone.0312335.ref001","first-page":"297193","article-title":"The autoimmune tautology: from polyautoimmunity and familial autoimmunity to the autoimmune genes","volume":"2012","author":"JM Anaya","year":"2012","journal-title":"Autoimmune Dis"},{"key":"pone.0312335.ref002","doi-asserted-by":"crossref","first-page":"102780","DOI":"10.1016\/j.jaut.2021.102780","article-title":"New insights into the taxonomy of autoimmune diseases based on polyautoimmunity","volume":"126","author":"M Rojas","year":"2022","journal-title":"J Autoimmun"},{"issue":"9935","key":"pone.0312335.ref003","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1016\/S0140-6736(13)61684-0","article-title":"Adrenal insufficiency","volume":"383","author":"E Charmandari","year":"2014","journal-title":"Lancet"},{"issue":"3","key":"pone.0312335.ref004","doi-asserted-by":"crossref","first-page":"305","DOI":"10.23736\/S0391-1977.17.02757-2","article-title":"Autoimmune endocrine diseases","volume":"43","author":"RM Ruggeri","year":"2018","journal-title":"Minerva Endocrinol"},{"issue":"5 Pt 2","key":"pone.0312335.ref005","first-page":"20R","article-title":"Monogenic autoimmune diseases: insights into self-tolerance","volume":"65","author":"MA Su","year":"2009","journal-title":"Pediatr Res"},{"issue":"4","key":"pone.0312335.ref006","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/intimm\/dxw002","article-title":"Genetics of autoimmune diseases: perspectives from genome-wide association studies","volume":"28","author":"Y. 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