A novel AIRE mutation leads to autoimmune polyendocrine syndrome type-1

Guofeng Qian; Xiaoyi Yan; Junli Xuan; Danfeng Zheng; Zhiwen He; Jianguo Shen

doi:10.3389/fcell.2022.948350

A novel AIRE mutation leads to autoimmune polyendocrine syndrome type-1

Front Cell Dev Biol. 2022 Aug 22:10:948350. doi: 10.3389/fcell.2022.948350. eCollection 2022.

Authors

Guofeng Qian¹, Xiaoyi Yan², Junli Xuan³, Danfeng Zheng⁴, Zhiwen He⁵, Jianguo Shen¹

Affiliations

¹ Department of Endocrinology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
² Department of Cell Biology, College of Medicine, Zhejiang University, Hangzhou, China.
³ Imaging Facility of Core Facilities, College of Medicine, Zhejiang University, Hangzhou, China.
⁴ Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
⁵ Department of Colorectal and Anal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Abstract

Autoimmune polyendocrine syndrome type-1 (APS-1) is a rare inherited monogenic autoimmune disease characterized by the presence of at least two of three following major clinical features: chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. Mutations in autoimmune regulator (AIRE) gene have been found to contribute to APS-1. In the present study, we reported a 36-years-old male APS-1 patient who presented with hypoparathyroidism and Addison's disease. The proband underwent complete clinical examinations and mutation screening was performed by Sanger sequencing on AIRE gene. A novel homozygous mutation in exon 9 of the AIRE gene (c.1024C>T) was identified. Based on sequencing findings, HEK293T cell-based assays were conducted to analyze the subcellular localization and mutant transcript processing. Our results revealed that p.Q342X mutant localized in nuclear speckles and exerted a dominant-negative effect on wildtype AIRE function. We reported the c.1024C>T mutation of AIRE gene for the first time, which enriched the AIRE mutation database and contributed to further understanding of APS-1.

Keywords: autoimmune polyendocrine syndrome type-1 (APS-1); autoimmune regulator (AIRE); exon; homozygous mutation; pedigree.