title: Clinical, functional, and genetic characterization of chronic granulomatous disease in 89 Turkish patients.
abstract: BACKGROUND
  Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytes resulting in impaired killing of bacteria and fungi. A mutation in one of the 4 genes encoding the components p22(phox), p47(phox), p67(phox), and p40(phox) of the leukocyte nicotinamide dinucleotide phosphate reduced (NADPH) oxidase leads to autosomal recessive (AR) CGD. A mutation in the CYBB gene encoding gp91(phox) leads to X-linked recessive CGD.
  
  
  OBJECTIVE
  The aim of this study is to show the correlation between clinical, functional, and genetic data of patients with CGD from Turkey.
  
  
  METHODS
  We report here the results of 89 patients with CGD from 73 Turkish families in a multicenter study.
  
  
  RESULTS
  Most of the families (55%) have an AR genotype, and 38% have an X-linked genotype; patients from 5 families with a suspected AR genotype (7%) were not fully characterized. We compared patients with CGD according to the severity of NADPH oxidase deficiency of neutrophils. Patients with A22(0), A67(0) or X91(0) phenotypes with a stimulation index of 1.5 or less have early clinical presentation and younger age at diagnosis (mean, 3.2 years). However, in p47(phox)-deficient cases and in 5 other AR cases with high residual oxidase activity (stimulation index ≥ 3), later and less severe clinical presentation and older age at diagnosis (mean, 7.1 years) were found. Pulmonary involvement was the most common clinical feature, followed by lymphadenitis and abscesses.
  
  
  CONCLUSIONS
  Later and less severe clinical presentation and older age at diagnosis are related to the residual NADPH oxidase activity of neutrophils and not to the mode of inheritance. CGD caused by A22(0) and A67(0) subtypes manifests as severe as the X91(0) subtype.
authors.affiliation: Immunology Department and GenKök Laboratory of Immunology, Faculty of Medicine, University of Erciyes, Kayseri, Turkey. Electronic address: mykoker@erciyes.edu.tr.
authors.forename: Mustafa Yavuz
authors.initials: MY
authors.lastname: Köker
authors.forename: Yıldız
authors.initials: Y
authors.lastname: Camcıoğlu
authors.forename: Karin
authors.initials: K
authors.lastname: van Leeuwen
authors.forename: Sara Şebnem
authors.initials: SŞ
authors.lastname: Kılıç
authors.forename: Işıl
authors.initials: I
authors.lastname: Barlan
authors.forename: Mustafa
authors.initials: M
authors.lastname: Yılmaz
authors.forename: Ayşe
authors.initials: A
authors.lastname: Metin
authors.forename: Martin
authors.initials: M
authors.lastname: de Boer
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Avcılar
authors.forename: Türkan
authors.initials: T
authors.lastname: Patıroğlu
authors.forename: Alişan
authors.initials: A
authors.lastname: Yıldıran
authors.forename: Olcay
authors.initials: O
authors.lastname: Yeğin
authors.forename: Ilhan
authors.initials: I
authors.lastname: Tezcan
authors.forename: Özden
authors.initials: Ö
authors.lastname: Sanal
authors.forename: Dirk
authors.initials: D
authors.lastname: Roos
mesh_terms: D002423:Cause of Death; D002675:Child, Preschool; D004789:Enzyme Activation; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000150:complications / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D006801:Humans; D015994:Incidence; D007239:Infections / Q000209:etiology; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D019255:NADPH Oxidases
keywords: A22 CGD with residual oxidase activity; A22(R); AR; Autosomal recessive; CGD; CYBA; CYBB; Chronic granulomatous disease; DHR; Dihydrorhodamine-1,2,3; MFI; Mean fluorescence intensity; NADPH; NBT; NCF1; NCF2; Nicotinamide dinucleotide phosphate reduced; Nitroblue tetrazolium; PMA; Phagocyte oxidase; Phorbol 12-myristate 13-acetate; ROI; Reactive oxygen intermediate; SI; Stimulation index; X-CGD; X-linked recessive chronic granulomatous disease; dihydrorhodamine-1,2,3 assay; mean fluorescence intensity; nicotinamide dinucleotide phosphate reduced oxidase; phox; stimulation index