A Novel Variant in the Stim1 Gene Leading to Combined Immunodeficiency and Congenital Myopathy

A Novel Variant in the Stim1 Gene Leading to Combined Immunodeficiency and Congenital Myopathy Publisher Pubmed

Taherkhani A¹ ; Gorjizad M¹ ; Ahmadabadi F² ; Saberi M³ ; Sharafian S⁴ ; Mesdaghi M⁴ ; Alavi S⁵ ; Sayari AA⁶ ; Abdolahzadeh S⁷ ; Seraj S⁷ ; Hassanipour H⁸ ; Chavoshzadeh Z⁹

Show Affiliations

1. Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2. Pediatric Neurology Department, Faculty of Medicine, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3. Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
4. Department of Immunology and Allergy, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5. Pediatric Congenital Hematologic Disorders Research Center, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
6. Department of Pediatric Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran
7. Department of Allergy and Clinical Immunology, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
8. School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
9. Immunology and Allergy Department, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Source: Immunologic Research Published:2025

Abstract

Stromal interaction molecule 1 (STIM1) is a transmembrane protein located in the endoplasmic and sarcoplasmic reticulum, where it plays a crucial role in activating calcium release-activated calcium (CRAC) channels. It functions as a calcium (Ca2⁺) sensor within the endoplasmic reticulum (ER), triggering CRAC channel opening and allowing calcium entry—mechanisms essential for maintaining intracellular calcium homeostasis. Mutations in the STIM1 gene that impair calcium signaling can disrupt both T cell and muscle cell function, leading to combined immunodeficiency and congenital myopathy. Here, we describe a 9-year-old boy with these clinical features, who was found to carry a previously undescribed mutation in the STIM1 gene. The patient presented with recurrent pneumonia, blood-streaked diarrhea, eczema, muscle weakness, and failure to thrive. Whole exome sequencing identified a novel homozygous missense variant in STIM1 (c.584T > C | p.Leu195Pro), considered likely pathogenic. This classification was supported by high Combined Annotation Dependent Depletion (CADD) and Rare Exome Variant Ensemble Learner (REVEL) scores of 29.8 and 0.89, respectively. Homozygosity of the mutation was confirmed using PCR-Sanger sequencing. This case highlights a novel homozygous STIM1 variant in a child with combined immunodeficiency and congenital myopathy. The clinical presentation is consistent with previously reported phenotypes associated with STIM1 deficiency. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.

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Style	Citing Format
MLA	Taherkhani A, et al.. "A Novel Variant in the Stim1 Gene Leading to Combined Immunodeficiency and Congenital Myopathy." Immunologic Research, vol. 73, no. 1, 2025, pp. -.
APA	Taherkhani A, Gorjizad M, Ahmadabadi F, Saberi M, Sharafian S, Mesdaghi M, Alavi S, Sayari AA, Abdolahzadeh S, Seraj S, Hassanipour H, Chavoshzadeh Z (2025). A Novel Variant in the Stim1 Gene Leading to Combined Immunodeficiency and Congenital Myopathy. Immunologic Research, 73(1), -.
Chicago	Taherkhani A, Gorjizad M, Ahmadabadi F, Saberi M, Sharafian S, Mesdaghi M, Alavi S, et al.. "A Novel Variant in the Stim1 Gene Leading to Combined Immunodeficiency and Congenital Myopathy." Immunologic Research 73, no. 1 (2025): -.
Harvard	Taherkhani A et al. (2025) 'A Novel Variant in the Stim1 Gene Leading to Combined Immunodeficiency and Congenital Myopathy', Immunologic Research, 73(1), pp. -.
Vancouver	Taherkhani A, Gorjizad M, Ahmadabadi F, Saberi M, Sharafian S, Mesdaghi M, et al.. A Novel Variant in the Stim1 Gene Leading to Combined Immunodeficiency and Congenital Myopathy. Immunologic Research. 2025;73(1):-.
BibTex	@article{ author = {Taherkhani A and Gorjizad M and Ahmadabadi F and Saberi M and Sharafian S and Mesdaghi M and Alavi S and Sayari AA and Abdolahzadeh S and Seraj S and Hassanipour H and Chavoshzadeh Z}, title = {A Novel Variant in the Stim1 Gene Leading to Combined Immunodeficiency and Congenital Myopathy}, journal = {Immunologic Research}, volume = {73}, number = {1}, pages = {-}, year = {2025} }
RIS	TY - JOUR AU - Taherkhani A AU - Gorjizad M AU - Ahmadabadi F AU - Saberi M AU - Sharafian S AU - Mesdaghi M AU - Alavi S AU - Sayari AA AU - Abdolahzadeh S AU - Seraj S AU - Hassanipour H AU - Chavoshzadeh Z TI - A Novel Variant in the Stim1 Gene Leading to Combined Immunodeficiency and Congenital Myopathy JO - Immunologic Research VL - 73 IS - 1 SP - EP - PY - 2025 ER -

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