Novel and recurrent mutations in the AIRE gene of autoimmune polyendocrinopathy syndrome type 1 (APS1) patients

Abstract

Autoimmune polyendocrinopathy syndrome type 1 (APS1) is characterized by the presence of at least two out of three clinical features, which include Addison's disease, hypoparathyroidism, and chronic mucocutaneous candidiasis. This disorder is caused by mutations in the AIRE (autoimmune regulator) gene. While several AIRE mutations have been described in APS1 patients of various ethnic origins, the genetic cause of APS1 in Arab patients requires further investigation. This study describes seven Arab families, in which 18 patients had APS1. In addition to the cardinal features of APS1, some patients exhibited alopecia, diabetes mellitus, nephrocalcinosis and other phenotypes associated with APS1. DNA sequencing of the AIRE gene of patients from this study identified four novel and one recurrent mutation. These mutations likely result in loss of AIRE function in the patients. In addition, it was noted that the non-pathogenic c.834C> G mutation (rs1800520, encoding for p.Ser278Arg) occurs with high incidence in the AIRE gene of Arab individuals. Furthermore, this investigation demonstrates inflammation of the hair follicles in APS1 patients with alopecia universalis. We conclude that Arab APS1 patients carry novel and recurrent mutations in the AIRE gene.

Autoimmune polyendocrine syndrome type 1 in an Indian cohort: a longitudinal study

“…Among these, p.R257X, p.R139X and p.R203X are founder mutations in Finland, Sardinia and Sicily, respectively (1, 11, 30), while p.C322fsX372 is frequent in many parts of Europe, United Kingdom and the USA (5, 7, 12, 27, 30, 31, 32). The other mutations have been reported as isolated cases (15, 31, 32). In contrast, both mutations (p.V80G and p.X546L+59aa) in patients from south India (of Dravidian ancestry) are not described in other ethnic groups.…”

“…The vast majority of studies on APS1 are in Caucasians of European origin, and data on other ethnic groups are scarce, consisting mainly of case reports (13, 14, 15). The Indian population is genetically complex, with ancestral gene pools, admixture due to migration and endogamy along lines of caste and sub-caste (16, 17).…”

Congenital Diarrheal Disorders: An Updated Diagnostic Approach

“…APS1 is another of the three codified autoimmune polyglandular syndromes with an autosomal recessive inheritance (even if a family with a dominant transmission was described) [47]. APS1 may be easily diagnosed searching for mutations in the autoimmune regulator (AIRE) gene encoding an autoimmune regulator (AIRE) protein [50,51]. To be noted that quite all affected patients have anti-interferon antibodies in serum.…”

Renal Failure Associated with APECED and Terminal 4q Deletion: Evidence of Autoimmune Nephropathy

“…The homozygous base pair insertion of cytosine at position 845 in our patient leads to a frame shift and a stop codon at amino acid 288 of the AIRE protein. It was previously reported only in one patient from Saudi Arabia who has APECED without renal involvement [24]. It has been hypothesized that renal autoantibodies could play a role in the initial development of chronic interstitial nephritis [8].…”