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Clinical, Immunological, and Molecular Findings of Patients with p47phox Defect Chronic Granulomatous Disease (CGD) in Indian Families

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Abstract

Chronic granulomatous disease (CGD) is a group of inherited disorder of phagocytes, resulting from mutations in the components of the NADPH oxidase complex. Reduced or absent oxygen radical synthesis seen in these patients leads to impaired killing of intracellular bacteria and fungi. CGD clinically presents with recurrent and life-threatening infections as well as granulomatous inflammatory responses. p47phox encoded by the NCF1 gene is the most common autosomal recessive form of CGD which is often clinically milder. Here, we are presenting the data on clinical and immunological findings in 21 Indian patients with Del GT mutation in the NCF1 gene. Diagnosis of these patients was based on detailed clinical evaluation, measurement of respiratory burst activity by nitro blue tetrazolium and dihydrorhodamine-1,2,3 assay, expression of p47phox by flow cytometry, and molecular confirmation by GeneScan method. Seventeen male and four female patients with median age of onset of 1 year ranging from 1.5 months to 6 years were included in the study. Sixty-two percent (13 out of 21) of patients belonged to a consanguineous marriage with only one family having a history of a previous sibling death. Significant variability in clinical presentation was observed in spite of identical genetic defect ranging from asymptomatic to very severe presentation leading to early death or requiring transplantation. However, none of these patients showed difference in immunological parameters to account for this variability. Thus, this study highlights the phenotypic heterogeneity seen in these patients with Del GT mutation in the NCF1 gene and its implication in management of these patients.

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Acknowledgment

We would like to thank the Foundation of Primary Immunodeficiency (FPID) for providing antibodies for NADPH oxidase components. We also thank Prof. Martin de Boer, Sanquin Blood Supply Foundation, Amsterdam, The Netherlands, for his valuable suggestions to study the molecular mutations in this cohort.

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Authors and Affiliations

  1. National Institute of Immunohaematology, Pediatric Immunology and Leukocyte Biology, 13th floor, KEM hospital campus, Mumbai, India

    Manasi Kulkarni, Maya Gupta, Aparna Dalvi & Manisha Madkaikar

  2. B. J Wadia Hospital for Children- Parel- Mumbai, Pediatric Hematology and Oncology, Mumbai, India

    Mukesh Desai, Prasad Taur & Ira Shah

  3. G. Kuppuswamy Naidu Memorial Hospital, Pediatric Pulomonology, Coimbatore, India

    Antony Terrance

  4. Narayana Health, Pediatric Hematologist and Oncologist, Bengalore, India

    Sunil Bhat

  5. Lokmanya Tilak Municipal General Hospital, Hematology-oncoloy, Mumbai, India

    Mamta Manglani

  6. Department of Pediatric Hematology, Oncology and BMT, Apollo Speciality Hospital, Chennai, Tamil Nadu, India

    Revathi Raj

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  1. Manasi Kulkarni
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Correspondence to Manisha Madkaikar.

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Kulkarni, M., Desai, M., Gupta, M. et al. Clinical, Immunological, and Molecular Findings of Patients with p47phox Defect Chronic Granulomatous Disease (CGD) in Indian Families. J Clin Immunol 36, 774–784 (2016). https://doi.org/10.1007/s10875-016-0333-y

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  • DOI: https://doi.org/10.1007/s10875-016-0333-y

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