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

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.

A Novel Homozygous Mutation of AIRE Gene in a Patient With Autoimmune Polyglandular Syndrome Type I

“…We described a patient with clinical criteria for APS1 and a novel homozygous AIRE gene mutation. She was diagnosed at a younger age when compared to other case reports in the literature [ 6 - 9 ], with de duad of chronic mucocutaneous candidiasis and symptomatic hypoparathyroidism, which are also the two most commonly reported manifestations [ 1 , 3 ]. At this point, Addison´s disease was absent but could appear later in the course of the disease, as has been described usually in older patients [ 3 ].…”

“…She also had a dental problems history with multiple consultations due to dental cavities. Ferre et al found that in an American cohort only 20% of the patients developed at least two of the three classic manifestations, so they proposed expanded diagnostic criteria, in which they included urticarial eruption, enamel hypoplasia, and intestinal malabsorption [ 6 ]. This alternative criterion could have helped to make an earlier diagnosis in our patient.…”

Addison’s Disease: Diagnosis and Management Strategies

“… 109 One study on APS-1 (11 patients from unrelated families of Iranian non-Jewish origin) identified 2 novel mutations: homozygous (c.308–1G>C), and a combination of 2 heterozygotes (c.1496delC + c.232T>C). 110 A post-mortem study on a potential eye donor with APS-1 harboring a mutation at R257X (C to T substitution) at exon 6 showed pigmentary deposits at the level of inner retinal vessels causing retinal atrophy, thus confirming retinitis pigmentosa as part of an APS-AD picture. 111 A novel AIRE mutation was identified in a 7-year-old girl with APS-1 complicated with AD-associated left ventricular systolic dysfunction.…”

Oral Candidiasis in Adult and Pediatric Patients with COVID-19

“…Among them, xerostomia and unsanitized dental prostheses are the main predisposing local factors, thus exposing the elderly and denture carriers to a higher risk of OC [ 2 , 3 , 4 , 5 ]. The most associated extra-oral conditions are related to age (mainly children and elderly) [ 6 ], bad habits such as smoking and poor oral hygiene [ 7 , 8 ], syndromic or genetic disorders [ 9 , 10 , 11 ] iatrogenic causes (broad-spectrum antibiotic therapy and the use of immunosuppressors and/or steroids) [ 12 ], and chronic and systemic diseases, such as diabetes mellitus and immunodeficiencies [ 13 , 14 ].…”