BACKGROUND: Autoimmune-polyendocrinopathy-candidiasis- ectodermal-distrophy (APECED) is a recessive disease, caused by mutations in the AutoImmune REgulator (AIRE) gene. Different mutations are peculiar of particular populations. In Italy, 3 hot spots areas where APECED shows an increased prevalence, have been identified in Sardinia, Apulia, and in the Venetian region.AIM: In this study, we analyzed AIRE mutations and genotype-phenotype correlation in APECED patients originating from Campania and in their relatives.PATIENTS AND METHODS: In 6 patients affected with APECED clinical findings, genetic analysis of AIRE, and APECED-related autoantibodies were performed.RESULTS: All patients carried at least 1 mutation on exon 1 or on splice-site flanking exon 1. Two siblings carried a complex homozygous mutation [IVS1 + 1G>C; IVS1 + 5delG] on intron 1; 2 patients were compound heterozygous for [T16M]+[W78R] (exons 1+2); 1 patient was compound heterozygous for [A21V]+[C322fs] (exons 1+8) and another was homozygous for [T16M]+[T16M] on exon 1. Expression of the disease showed wide variability while circulating autoantibodies paralleled to phenotype in each patient. Analysis of relatives allowed the identification of 8 heterozygotes. None of heterozygous subjects presented major findings of APECED.CONCLUSIONS: Mutations localized on exon 1 and the region flanking exon 1 are common in APECED patients originating from Campania. Genotype-phenotype correlation failed to reveal a relationship between detected mutations and clinical expression. Mutations in heterozygosis in AIRE gene are not associated to major findings of APECED.
Molecular Background and genotype-phenotype correlation in APECED patients from Campania and in their relatives / Capalbo, Donatella; Mazza, C.; Giordano, R.; Improda, N.; Arvat, E.; Cervato, S.; Morlin, L.; Pignata, Claudio; Betterle, C.; Salerno, Mariacarolina. - In: JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION. - ISSN 1720-8386. - 35:2(2012), pp. 169-173. [10.3275/7677]
Molecular Background and genotype-phenotype correlation in APECED patients from Campania and in their relatives.
CAPALBO, DONATELLA;PIGNATA, CLAUDIO;SALERNO, MARIACAROLINA
2012
Abstract
BACKGROUND: Autoimmune-polyendocrinopathy-candidiasis- ectodermal-distrophy (APECED) is a recessive disease, caused by mutations in the AutoImmune REgulator (AIRE) gene. Different mutations are peculiar of particular populations. In Italy, 3 hot spots areas where APECED shows an increased prevalence, have been identified in Sardinia, Apulia, and in the Venetian region.AIM: In this study, we analyzed AIRE mutations and genotype-phenotype correlation in APECED patients originating from Campania and in their relatives.PATIENTS AND METHODS: In 6 patients affected with APECED clinical findings, genetic analysis of AIRE, and APECED-related autoantibodies were performed.RESULTS: All patients carried at least 1 mutation on exon 1 or on splice-site flanking exon 1. Two siblings carried a complex homozygous mutation [IVS1 + 1G>C; IVS1 + 5delG] on intron 1; 2 patients were compound heterozygous for [T16M]+[W78R] (exons 1+2); 1 patient was compound heterozygous for [A21V]+[C322fs] (exons 1+8) and another was homozygous for [T16M]+[T16M] on exon 1. Expression of the disease showed wide variability while circulating autoantibodies paralleled to phenotype in each patient. Analysis of relatives allowed the identification of 8 heterozygotes. None of heterozygous subjects presented major findings of APECED.CONCLUSIONS: Mutations localized on exon 1 and the region flanking exon 1 are common in APECED patients originating from Campania. Genotype-phenotype correlation failed to reveal a relationship between detected mutations and clinical expression. Mutations in heterozygosis in AIRE gene are not associated to major findings of APECED.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.