title: X-linked chronic granulomatous disease in a male child with an X-CGD carrier, Klinefelter brother.
abstract: BACKGROUND
  Chronic granulomatous disease (CGD) is a rare primary immunodeficiency (PID) caused by a dysfunctional respiratory burst enzyme NADPH-oxidase. The concurrence of Klinefelter's Syndrome (KS) and CGD would be extremely rare.
  
  
  OBJECTIVE
  We describe the study of a family where the youngest male child had X-linked CGD (X-CGD) while his older brother was both an X-CGD carrier and a Klinefelter.
  
  
  METHODS
  Flow cytometry was used to study respiratory burst and gp91-phox expression, while genetic investigation was done by RT-PCR, PCR and X-chromosome short tandem repeat (X-STR) analysis.
  
  
  RESULTS
  The Dihydrorhodamine (DHR) assay showed the patient's neutrophils failed to produce a respiratory burst, while both the mother and an older brother showed a bimodal response. gp91-phox expression was absent in the patient's neutrophils, and bimodal in the mother's and brother's neutrophils. The patient's cDNA showed a C>T change at nucleotide 676 of the CYBB gene. The same change was seen in the patient's gDNA, while the brother and mother were heterozygous, with C and T, in this position. The c.676C>T is a nonsense mutation that leads to premature termination of the gp91-phox protein. The brother karyotyped as 47, XXY and X chromosome analysis showed that he had inherited both his mother's X chromosomes.
  
  
  CONCLUSIONS
  This study showed that the patient had gp91-phox deficient CGD while his older brother was a CGD carrier and a Klinefelter, who had inherited both his mother's X chromosomes. This is the first report of such a concurrence in an individual, and argues for family members to be included in PID studies.
authors.affiliation: Institute for Medical Research, Jalan Pahang, Kuala Lumpur, Malaysia. gillhk@imr.gov
authors.forename: Harvindar Kaur
authors.initials: HK
authors.lastname: Gill
authors.forename: Hemahwathy Chanthira
authors.initials: HC
authors.lastname: Kumar
authors.forename: Chan Kwai
authors.initials: CK
authors.lastname: Cheng
authors.forename: Choo Chong
authors.initials: CC
authors.lastname: Ming
authors.forename: Revathy
authors.initials: R
authors.lastname: Nallusamy
authors.forename: Narazah Mohd
authors.initials: NM
authors.lastname: Yusoff
authors.forename: Saharuddin B
authors.initials: SB
authors.lastname: Mohamad
authors.forename: Adiratna Mat
authors.initials: AM
authors.lastname: Ripen
authors.forename: Jasbir Singh
authors.initials: JS
authors.lastname: Dhaliwal
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Murad
mesh_terms: D000328:Adult; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000201:enzymology / Q000235:genetics*; D006105:Granulomatous Disease, Chronic / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007223:Infant; D007713:Klinefelter Syndrome / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D018895:Microsatellite Repeats; D009035:Mothers; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000096:biosynthesis / Q000235:genetics; D010375:Pedigree; D016897:Respiratory Burst / Q000235:genetics; D035781:Siblings
chemical_list: D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases