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Mutational analysis in different genes underlying severe combined immunodeficiency in seven consanguineous Pakistani families

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Abstract

Background

Severe Combined Immunodeficiency (SCID) is an autosomal recessive inborn error of immunity (IEI) characterized by recurrent chest and gastrointestinal (GI) infections and in some cases associated with life-threatening disorders.

Methodology and results

This current study aims to unwind the molecular etiology of SCID and also extended the patients’ phenotype associated with identified particular variants. Herein, we present 06 disease-causing variants identified in 07 SCID-patients in three different SCID related genes. Whole Exome Sequencing (WES) followed by Sanger Sequencing was employed to explore genetic variations. The results included identification of two previously reported heterozygous variants in homozygous form for the first time in RAG1gene [(p.Arg410Gln);(p.Arg737His)], followed by a recurrent variant (p.Trp959*) in RAG1, a novel variant in IL2RG (p.Asp48Lfs*24), a recurrent variant in IL2RG (p.Gly271Glu) and a recurrent variant in DCLRE1C (p.Arg191*) gene.

Conclusion

To conclude, the immune-profiling and WES revealed two novel, two as homozygous state for the first time, and two recurrent disease causing variants contributing valuably to our existing knowledge of SCID.

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Data availability

Data will be provided upon request.

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Funding

The authors (Hajra Fayyaz and Atteaya Zaman) were supported by IRSIP fellowships from Higher Education Commission (HEC), Islamabad, Pakistan.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan

    Hajra Fayyaz, Atteaya Zaman, Wasim Ahamad & Imran Ullah

  2. Department of Biochemistry, Federal Medical & Dental College, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan

    Atteaya Zaman

  3. Forensic Medicine & Toxicology, School of Health Sciences, National University of Sciences and Technology, Islamabad, Pakistan

    Sheeba Shabbir

  4. Department of Biochemistry, HBS Medical & Dental College, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan

    Zara Khalid Khan

  5. Department of Pediatrics, Pakistan Institute of Medical Sciences Islamabad, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan

    Nighat Haider

  6. Department of Paediatrics & Paediatrics Infections Disease, Agha Khan University Hospital, Karachi, Pakistan

    Ali Faisal Saleem

Authors
  1. Hajra Fayyaz
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  2. Atteaya Zaman
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  3. Sheeba Shabbir
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  4. Zara Khalid Khan
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  5. Nighat Haider
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  6. Ali Faisal Saleem
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  7. Wasim Ahamad
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  8. Imran Ullah
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Contributions

Hajra Fayyaz and Atteaya Zaman collected blood samples, performed experimental work and prepared the manuscript. Sheeba Shabbir, Zara Khalid, Nighat Haider, and Ali Faisal Saleem identified the families and help in diagnosis of disease phenotypes. Wasim Ahmad and Imran Ullah designed the study, provided funds and finalized the manuscript.

Corresponding author

Correspondence to Imran Ullah.

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Competing interests

The authors declare no competing interest.

Ethical approval

The research study was approved by Institutional Review Board (IRB), Quaid-i-Azam University, Islamabad, Pakistan under ethical committee approval number ‘IRB-QA-176’. Informed written consent was taken from participating members of families. Blood sampling from normal and affected individuals were carried out according to guidelines provided by Declaration of Helsinki.

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Fayyaz, H., Zaman, A., Shabbir, S. et al. Mutational analysis in different genes underlying severe combined immunodeficiency in seven consanguineous Pakistani families. Mol Biol Rep 51, 302 (2024). https://doi.org/10.1007/s11033-024-09222-0

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