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.
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Data availability
The data that support the findings of this study are available on request from the corresponding author.
Change history
03 December 2022
A Correction to this paper has been published: https://doi.org/10.1007/s40618-022-01965-6
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Acknowledgements
we thank Dr Lan Guyen, Department of Medical Genomics, Royal Prince Lafred Hospital, Camperdown, Australia, for revising the English version of the manuscript
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RG, FR and LS followed the patients up. GN performed the genetic analysis. PA evaluated the antibodies, BC and RG wrote the paper. All authors critically reviewed and edited the manuscript, and approved the final version as submitted.
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No author has any financial or non-financial interests that are directly or indirectly related to the work submitted for publication.
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Patient consents were obtained from all individuals from whom identifiable data are presented. This case report was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. The paper is exempt from ethical committee approval. Ethical approval was not required for this study in accordance with national guidelines.
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Radetti, G., Puel, A., Franceschi, R. et al. A non-classical presentation of APECED in a family with heterozygous R203X AIRE gene mutation. J Endocrinol Invest 46, 629–632 (2023). https://doi.org/10.1007/s40618-022-01937-w
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DOI: https://doi.org/10.1007/s40618-022-01937-w