title: Clinical, Immunological, and Molecular Findings of Patients with p47phoxDefect Chronic Granulomatous Disease (CGD) in Indian Families.
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. p47phoxencoded 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 p47phoxby 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.
authors.affiliation: National Institute of Immunohaematology, Pediatric Immunology and Leukocyte Biology, 13th floor, KEM hospital campus, Mumbai, India.
authors.forename: Manasi
authors.initials: M
authors.lastname: Kulkarni
authors.affiliation: B. J Wadia Hospital for Children- Parel- Mumbai, Pediatric Hematology and Oncology, Mumbai, India.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Desai
authors.affiliation: National Institute of Immunohaematology, Pediatric Immunology and Leukocyte Biology, 13th floor, KEM hospital campus, Mumbai, India.
authors.forename: Maya
authors.initials: M
authors.lastname: Gupta
authors.affiliation: National Institute of Immunohaematology, Pediatric Immunology and Leukocyte Biology, 13th floor, KEM hospital campus, Mumbai, India.
authors.forename: Aparna
authors.initials: A
authors.lastname: Dalvi
authors.affiliation: B. J Wadia Hospital for Children- Parel- Mumbai, Pediatric Hematology and Oncology, Mumbai, India.
authors.forename: Prasad
authors.initials: P
authors.lastname: Taur
authors.affiliation: G. Kuppuswamy Naidu Memorial Hospital, Pediatric Pulomonology, Coimbatore, India.
authors.forename: Antony
authors.initials: A
authors.lastname: Terrance
authors.affiliation: Narayana Health, Pediatric Hematologist and Oncologist, Bengalore, India.
authors.forename: Sunil
authors.initials: S
authors.lastname: Bhat
authors.affiliation: Lokmanya Tilak Municipal General Hospital, Hematology-oncoloy, Mumbai, India.
authors.forename: Mamta
authors.initials: M
authors.lastname: Manglani
authors.affiliation: Department of Pediatric Hematology, Oncology and BMT, Apollo Speciality Hospital, Chennai, Tamil Nadu, India.
authors.forename: Revathi
authors.initials: R
authors.lastname: Raj
authors.affiliation: B. J Wadia Hospital for Children- Parel- Mumbai, Pediatric Hematology and Oncology, Mumbai, India.
authors.forename: Ira
authors.initials: I
authors.lastname: Shah
authors.affiliation: National Institute of Immunohaematology, Pediatric Immunology and Leukocyte Biology, 13th floor, KEM hospital campus, Mumbai, India. madkaikarmanisha@gmail.com.
authors.forename: Manisha
authors.initials: M
authors.lastname: Madkaikar
mesh_terms: D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics; D019255:NADPH Oxidases / Q000235:genetics* / Q000276:immunology; D010586:Phagocytes / Q000276:immunology; D016897:Respiratory Burst / Q000235:genetics / Q000276:immunology
chemical_list: D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1
keywords: AR-CGD; GeneScan; NCF1 defect; p47Phox flow cytometry