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Molecular and Clinical Characterization of Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Syndrome (Apeced) in Iranian Non-Jewish Patients: Report of Two Novel Aire Gene Pathogenic Variants Publisher Pubmed



Setoodeh A1 ; Panjehshahi S2 ; Bahmani F1 ; Vandrajabpour F3 ; Jalilian N4 ; Sayarifard F1 ; Abbasi F1 ; Sayarifard A5 ; Rostami P1 ; Parvaneh N6 ; Akhavanniaki H7 ; Ahmadifard M7 ; Tabrizi M3
Authors
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Authors Affiliations
  1. 1. Division of Endocrinology and Metabolism, Growth and Development Research Center, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  3. 3. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
  5. 5. Growth and Development Research Center, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Division of Allergy and Clinical Immunology, Department of Pediatrics, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Medical Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran

Source: Orphanet Journal of Rare Diseases Published:2022


Abstract

Objective: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) is a rare autosomal recessive systemic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Incidence of this genetic disorder is estimated at 1/90,000–200,000 worldwide and 1/6500–9000 in genetically isolated populations such as Iran. Here, we investigated AIRE gene mutations in eight independent Iranian non-Jewish families. Methods: We sequenced the coding regions of the AIRE gene and documented mutations which were further confirmed in respective parents. Results: In total, 11 cases from 8 independent families were recruited. Mucosal candidiasis, Addison’s disease and hypoparathyroidism were the most common clinical manifestations in these patients. One novel homozygous splice acceptor mutation (c.308-1G>C), and one novel heterozygous stop-gain mutation (c.1496delC) combined with a known heterozygous c.232T>C missense mutation were found. Moreover, we observed previously described splice donor (c.1095+2T>A), frameshift (c.967-979del), stop-gain (c.415C>T), and missense (c.62C>T) mutations among the patients. All results were co-segregated in parents. Conclusion: Here, we reported two novel mutations in the AIRE gene leading to APECED. Our data could provide insight into the phenotypic and genotypic spectrum of APECED in the non-Jewish Iranian population. These findings, in addition to future functional assays, can elucidate disease-causing mechanisms related to the AIRE gene and assist in genetic counseling and diagnosis. © 2022, The Author(s).
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