BCL10 loss-of-function novel mutation leading to atypical severe combined immunodeficiency

Salem Al-Tamemi; Zaid Alhinai; Najwa Al-Rahbi; Raghad Al-Abdawani; Laila Al-Yazidi; Jalila Al-Shekaili; Mahmood Al-Kindi; Almundher Al-Maawali

doi:10.1016/j.clim.2022.109067

BCL10 loss-of-function novel mutation leading to atypical severe combined immunodeficiency

Clin Immunol. 2022 Aug:241:109067. doi: 10.1016/j.clim.2022.109067. Epub 2022 Jun 22.

Authors

Salem Al-Tamemi¹, Zaid Alhinai², Najwa Al-Rahbi², Raghad Al-Abdawani², Laila Al-Yazidi², Jalila Al-Shekaili³, Mahmood Al-Kindi³, Almundher Al-Maawali⁴

Affiliations

¹ Department of Child Health, Sultan Qaboos University Hospital, Muscat, Oman. Electronic address: tamemi@squ.edu.om.
² Department of Child Health, Sultan Qaboos University Hospital, Muscat, Oman.
³ Department of Microbiology & Immunology, Sultan Qaboos University Hospital, Muscat, Oman.
⁴ Department of Clinical Genetics, Sultan Qaboos University Hospital, Department of Genetics, College of Medicine and Health Sciences, Muscat, Oman.

PMID: 35750252
DOI: 10.1016/j.clim.2022.109067

Abstract

Background: Severe combined immunodeficiency (SCID) is characterized by severe, early-onset infection in infants. B-cell lymphoma/leukemia (BCL) 10 defects causing SCID have been reported previously in two patients.

Material & methods: A seven-month-old female infant was admitted with bilateral pneumonia requiring ventilatory support. She had a history of recurrent infections starting from four months of age. The patient was investigated for primary immunodeficiency.

Results: Immunological investigations revealed hypogammaglobulinemia with normal CD4 and CD8 lymphocyte counts, while a lymphocyte proliferation assay showed absent response to phytohemagglutinin stimulation, thereby establishing the diagnosis of an atypical form of SCID. Genetic testing revealed a homozygous mutation in the BCL10 gene, with both parents demonstrating a heterozygous state (NM_003921.5:c.271A > C:p.[Thr91Pro]). The patient died before bone marrow transplantation due to severe disseminated adenovirus disease.

Conclusion: We report the first patient from the Middle East with a novel homozygous mutation in the BCL10 gene causing SCID.

Keywords: Adenovirus; BCL10; Hypogammaglobulinemia; Oman; Severe combined immunodeficiency.

MeSH terms

B-Cell CLL-Lymphoma 10 Protein / genetics
Female
Genetic Testing
Homozygote
Humans
Infant
Mutation
Severe Combined Immunodeficiency* / diagnosis
Severe Combined Immunodeficiency* / genetics
Severe Combined Immunodeficiency* / therapy

Substances

B-Cell CLL-Lymphoma 10 Protein
BCL10 protein, human

Supplementary concepts

Severe combined immunodeficiency, atypical