R Giorgio1, P Anne2, F Roberto3, L Silvia4, G Nicoletta5, B Corrado6. 1. Department of Pediatrics, Regional Hospital, Lorenz Böhler 5, 39100, Bolzano, Italy. giorgio.radetti@gmail.com. 2. Laboratory of Human Genetics of Infectious Diseases, INSERM UMR 1163, University of Paris, Imagine Institute, Paris, France. 3. Division of Paediatrics, S. Chiara General Hospital, Trento, Italy. 4. Department of Pediatrics, Regional Hospital, Lorenz Böhler 5, 39100, Bolzano, Italy. 5. Unit of Laboratory Medicine, Department of Medicine, University of Padua, Padua, Italy. 6. Endocrine Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy.
Abstract
PURPOSE: Biallelic loss-of-function mutations of AIRE cause the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome. However, single nucleotide mutations may cause a milder phenotype. In this paper, we describe an unusual and mild phenotype in a mother and her two children (son and daughter) who carry a rare heterozygous mutation of AIRE. METHODS AND RESULTS: The son presented with alopecia and subclinical hypothyroidism due to Hashimoto's Thyroiditis (HT); the daughter had alopecia, vaginal mycosis, stomach pains and subclinical hypothyroidism due to HT; and the mother had alopecia, vaginal mycosis and stomach pains. Organ- and non-organ-specific autoantibodies were evaluated as well as antibodies against interleukin-17A, -17F, -22 (IL-Abs) and interferon -α and -ω (IFN-Abs). The organ- and non-organ-specific autoantibodies screening was negative in the son, while the daughter was positive for liver-kidney microsomal antibodies (LKMAbs) and the mother was positive for glutamic acid decarboxylase antibodies (GADAbs). Daughter and mother were also positive for IFN-Abs. Analysis of the AIRE gene identified a rare heterozygous R203X mutation in all three family members. CONCLUSIONS: We describe for a first time a family with heterozygous R203X AIRE mutation causing an APECED-like condition, as confirmed by presence of IFN-Abs. The unusual mild phenotype should be reassuring for the patients and assist in their clinical management.
PURPOSE: Biallelic loss-of-function mutations of AIRE cause the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome. However, single nucleotide mutations may cause a milder phenotype. In this paper, we describe an unusual and mild phenotype in a mother and her two children (son and daughter) who carry a rare heterozygous mutation of AIRE. METHODS AND RESULTS: The son presented with alopecia and subclinical hypothyroidism due to Hashimoto's Thyroiditis (HT); the daughter had alopecia, vaginal mycosis, stomach pains and subclinical hypothyroidism due to HT; and the mother had alopecia, vaginal mycosis and stomach pains. Organ- and non-organ-specific autoantibodies were evaluated as well as antibodies against interleukin-17A, -17F, -22 (IL-Abs) and interferon -α and -ω (IFN-Abs). The organ- and non-organ-specific autoantibodies screening was negative in the son, while the daughter was positive for liver-kidney microsomal antibodies (LKMAbs) and the mother was positive for glutamic acid decarboxylase antibodies (GADAbs). Daughter and mother were also positive for IFN-Abs. Analysis of the AIRE gene identified a rare heterozygous R203X mutation in all three family members. CONCLUSIONS: We describe for a first time a family with heterozygous R203X AIRE mutation causing an APECED-like condition, as confirmed by presence of IFN-Abs. The unusual mild phenotype should be reassuring for the patients and assist in their clinical management.
Authors: S Garelli; M Dalla Costa; C Sabbadin; S Barollo; B Rubin; R Scarpa; S Masiero; A Fierabracci; C Bizzarri; A Crinò; M Cappa; M Valenzise; A Meloni; A M De Bellis; C Giordano; F Presotto; R Perniola; D Capalbo; M C Salerno; A Stigliano; G Radetti; V Camozzi; N A Greggio; F Bogazzi; I Chiodini; U Pagotto; S K Black; S Chen; B Rees Smith; J Furmaniak; G Weber; F Pigliaru; L De Sanctis; C Scaroni; C Betterle Journal: J Endocrinol Invest Date: 2021-05-18 Impact factor: 4.256