Novel Gene Mutations Regulating Immune Responses in Autoimmune Polyglandular Syndrome With an Atypical Course

Author:

Yukina Marina1ORCID,Erofeeva Taisia2,Nuralieva Nurana1,Andreeva Tatiana23,Savvateeva Elena4,Dudko Natalia2,Troshina Ekaterina1,Rogaev Evgeny2356,Melnichenko Galina1

Affiliation:

1. Endocrinology Research Centre, Moscow 117036, Russia

2. Laboratory of Evolutionary genomics, Department of Genomics and Human Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia

3. Center for Genetics and Genetic Technologies, Faculty of Biology, Lomonosov Moscow State University, Moscow 119192, Russia

4. Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia

5. Center for Genetics and Life Science, Sirius University of Science and Technology, Sochi 354340, Russia

6. Department of Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts 01604, USA

Abstract

Abstract Context Autoimmune polyglandular syndrome (APS) is a cluster of endocrine disorders arising from immune dysregulation, often combined with damage to nonendocrine organs. There are 2 types of APS: type 1 and type 2 (APS-1 and APS-2, respectively). In clinical practice, an atypical course of APS is often observed. Objective This work aims to find a novel genetic predictor of APS. Methods We performed exome sequencing in 2 patients with an atypical clinical APS picture and members of their families. Patient A presented with a manifestation of APS-2 in early childhood and patient B with a late manifestation of the main components of APS-1. Results In patient B, we identified inherited compound mutations as a novel combination of the c.769C > T and c.821delG alleles of AIRE and genetic variation in the CIITA gene. No homozygous or compound mutations in AIRE were found in patient A, but we did reveal mutations in genes encoding regulatory proteins of innate and acquired immunity in this patient. Conclusion Our data revealed novel combination of mutations in the AIRE gene in atypical APS and imply that mutations in immune-related genes may modify the clinical manifestation of APS in AIRE-mutation carriers and contribute to the development of autoimmune pathology in non-AIRE carriers with atypical APS.

Funder

Ministry of Science and Higher Education of the Russian Federation

Publisher

The Endocrine Society

Subject

Endocrinology, Diabetes and Metabolism

Reference43 articles.

1. Autoimmune polyglandular syndromes;Sperling,2000

2. Autoimmune polyendocrine syndromes;Husebye;N Engl J Med.,2018

3. Autoimmune polyglandular syndromes: interplay between the immune and the endocrine systems leading to a diverse set of clinical diseases and new insights into immune regulation;Lebovitz;Diabetes Technol Ther.,2013

4. Autoimmune polyglandular syndrome type 2: an unusual presentation;Karamifar;Acta Med Iran.,2010

5. Peculiarities of autoimmune polyglandular syndromes in children and adolescents;Zirilli;Acta Biomed.,2017

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