Digenic inheritance of IL-36RA and SEC61A1 mutations underlies generalized pustular psoriasis with hypogammaglobulinemia

Abduarahman Almutairi; Maha M Amin; Mohamed A M Rashwan; Marwa H Elnagdy; Ragheed Rizk; Sara A Bahgat; Craig D Platt; Ali Sobh

doi:10.1016/j.clim.2022.108930

Digenic inheritance of IL-36RA and SEC61A1 mutations underlies generalized pustular psoriasis with hypogammaglobulinemia

Clin Immunol. 2022 Feb:235:108930. doi: 10.1016/j.clim.2022.108930. Epub 2022 Jan 19.

Authors

Abduarahman Almutairi¹, Maha M Amin², Mohamed A M Rashwan³, Marwa H Elnagdy⁴, Ragheed Rizk⁵, Sara A Bahgat⁶, Craig D Platt⁷, Ali Sobh⁸

Affiliations

¹ Department of Pediatrics, Security Forces Hospital Program, Riyadh, Saudi Arabia; Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States. Electronic address: abhalmutairi@sfh.med.sa.
² Department of Pathology, Faculty of Medicine, Mansoura University, Egypt.
³ Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Egypt.
⁴ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Egypt.
⁵ Intern at Mansoura University Hospitals, Faculty of Medicine, Mansoura University, Egypt.
⁶ Resident in Pediatrics, Mansoura Specialized Hospital, Mansoura, Egypt.
⁷ Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States.
⁸ Department of Pediatrics, Mansoura University Children's Hospital, Faculty of Medicine, Mansoura University, Mansoura, Egypt. Electronic address: ali.sobh@mans.edu.eg.

PMID: 35063669
DOI: 10.1016/j.clim.2022.108930

Abstract

We report a female patient presenting with generalized pustular psoriasis and hypogammaglobulinemia due to digenic mutations in IL-36RA and SEC61A1. The patient presented with recurrent fevers, elevated inflammatory markers, hepatosplenomegaly, and recurrent sinopulmonary infections in the context of hypogammaglobulinemia which improved on immunoglobulin replacement. This report demonstrates how digenic inheritance leads to complex phenotypes, and illustrates the importance of following an unbiased approach to identifying variants, especially in patients with atypical clinical presentations.

Keywords: DITRA; Generalized pustular psoriasis; Hypogammaglobulinemia; IL-36RA; SEC61A1.

Publication types

Case Reports

MeSH terms

Agammaglobulinemia / genetics*
Agammaglobulinemia / pathology
Child, Preschool
Consanguinity
Female
Genetic Predisposition to Disease*
Humans
Interleukins / genetics*
Mutation
Pedigree
Psoriasis / genetics*
Psoriasis / pathology
SEC Translocation Channels / genetics*

Substances

IL36RN protein, human
Interleukins
SEC Translocation Channels
SEC61A1 protein, human