Identification of two novel mutations in the first Sicilian APECED patient with no R203X mutation in AIRE gene and review of Italian APECED genotypes

Valenzise, Mariella; Wasniewska, Malgorzata; Mirabelli, Silvestro; Luca, Filippo De; Cervato, Sara; Betterle, Corrado

doi:10.1016/j.gene.2012.03.032

Cited by 11 publications

(15 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regarding other A-AD forms, isolated A-AD showed an increment of DRB1*03 near statistical significance, but the small number of patients studied in this group may be a limiting factor. Almost all patients with APS1 in our survey (96%) had AIRE gene mutations, in agreement with previous studies (33,35,36,37,38); no correlation with class II HLA alleles was detected in this group.…”

Section: Discussionsupporting

confidence: 93%

Addison's disease: a survey on 633 patients in Padova

Betterle

Scarpa

Garelli

et al. 2013

European Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

Objective: Addison's disease (AD) is a rare endocrine condition. Design: We aimed to evaluate clinical, immunologic, adrenal imaging, and genetic features in 633 Italian patients with AD followed up since 1967. Methods: Adrenal cortex autoantibodies, presence of other autoimmune and nonautoimmune diseases, nonadrenal autoantibodies, adrenal imaging, and genetic profile for HLA-DRB1 and AIRE were analyzed. Results: A total of 492 (77.7%) patients were found to be affected by autoimmune AD (A-AD), 57 (9%) tuberculous AD, 29 (4.6%) genetic-associated AD, 10 (1.6%) adrenal cancer, six (0.94%) post-surgical AD, four (0.6%) vascular disorder-related AD, three (0.5%) post-infectious AD, and 32 (5.1%) were defined as idiopathic. Adrenal cortex antibodies were detected in the vast majority (88-100%) of patients with recent onset A-AD, but in none of those with nonautoimmune AD. Adrenal imaging revealed normal/atrophic glands in all A-AD patients: 88% of patients with A-AD had other clinical or subclinical autoimmune diseases or were positive for nonadrenal autoantibodies. Based on the coexistence of other autoimmune disorders, 65.6% of patients with A-AD were found to have type 2 autoimmune polyendocrine syndrome (APS2), 14.4% have APS1, and 8.5% have APS4. Class II HLA alleles DRB1*03 and DRB1*04 were increased, and DRB1*01, DRB1*07, DRB1*013 were reduced in APS2 patients when compared with controls. Of the patients with APS1, 96% were revealed to have AIRE gene mutations. Conclusions: A-AD is the most prevalent form of adrenal insufficiency in Italy, and w90% of the patients are adrenal autoantibody-positive at the onset. Assessment of patients with A-AD for the presence of other autoimmune diseases should be helpful in monitoring and diagnosing APS types 1, 2, or 4 and improving patients' care.

show abstract

Section: Discussionsupporting

confidence: 93%

Addison's disease: a survey on 633 patients in Padova

Betterle

Scarpa

Garelli

et al. 2013

European Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Another patient (No. 15) exhibited 2 different mutations (S107C and Q108fs), which have been specifically described elsewhere [10]. …”

Section: Resultsmentioning

confidence: 99%

“…The first 7 patients included in table 1 are those who are being described for the first time in the present report, whereas cases 8-15 have been already reported elsewhere [7,8,9,10,11]; the respective references are also detailed in table 1.…”

Section: Methodsmentioning

confidence: 97%

“…In the Sicilian population, only 8 patients have been identified to date, and are described elsewhere [7,8,9,10,11]. In 56% of the alleles, the authors found the rare mutation of the AIRE gene R203X, which has been considered to date as pathognomonic of Sicilian APECED patients [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…In 56% of the alleles, the authors found the rare mutation of the AIRE gene R203X, which has been considered to date as pathognomonic of Sicilian APECED patients [10,11]. …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy: Report of Seven Additional Sicilian Patients and Overview of the Overall Series from Sicily

Valenzise

Fierabracci²,

Cappa

et al. 2014

Horm Res Paediatr

Self Cite

View full text Add to dashboard Cite

Background: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive inherited disease caused by the mutation of the AIRE gene on chromosome 21. To date, 8 Sicilian patients have been described and the R203X AIRE mutation was found to be the most common in this region. Aims: (1) To describe 7 additional Sicilian APECED patients and to review all 15 Sicilian APECED patients who have been investigated by our group in the last years, and (2) to report a novel AIRE gene mutation. Results: Among the 3 cardinal features of APECED, hypoparathyroidism has been already detected in all 15 patients, whereas Addison's disease and chronic mucocutaneous candidiasis have so far been found in 10/15 and 12/15 cases, respectively. In 2 consanguineous cases, AIRE gene analysis revealed a novel mutation, named IVS13+2T, in homozygosis. R203X was the most common mutation in this region (30% of alleles and 46.6% of patients), followed by R257X (20% of alleles and 40% of patients). Conclusions: Sicilian APECED patients are confirmed to have some peculiar characteristics from a clinical and genetic point of view. No correlations between genotype and phenotype were identified.

show abstract

Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients

Garelli

Costa

Sabbadin

et al. 2021

J Endocrinol Invest

View full text Add to dashboard Cite

Background Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison’s disease (AD). Methods Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined. Results The prevalence of APS-1 was 2.6 cases/million (range 0.5–17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases. Conclusions In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.

show abstract

Identification of two novel mutations in the first Sicilian APECED patient with no R203X mutation in AIRE gene and review of Italian APECED genotypes

Cited by 11 publications

References 26 publications

Addison's disease: a survey on 633 patients in Padova

Addison's disease: a survey on 633 patients in Padova

Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy: Report of Seven Additional Sicilian Patients and Overview of the Overall Series from Sicily

Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients

Contact Info

Product

Resources

About