title: Nonsense mutations of the CYBB gene in two Thai families with X-linked chronic granulomatous disease.
abstract: X-linked chronic granulomatous disease (X-CGD) is an immunodeficiency disorder characterized by defective intracellular killing of microorganisms due to the neutrophils' inability to generate superoxide ions. Although it is always caused by mutations in the CYBB gene, clinical and molecular characteristics vary in different ethnic backgrounds. Two unrelated Thai boys presented with severe persistent pulmonary infections at the age of two months. Their abnormal dihydrorhodamine (DHR) flow cytometry assays supported the diagnosis of X-CGD. Mutation analysis was performed by polymerase chain reaction (PCR) amplification and sequencing of the entire coding regions of CYBB. Mutations identified were confirmed by restriction enzyme analyses. PCR-sequencing of the entire coding regions of CYBB identified nonsense mutations, 271C>T (R91X) in exon 4 and 456T>A (Y152X) in exon 5, in probands of each family. Both of the patients' mothers were found to be carriers. This observation supports that CYBB is the gene responsible for X-CGD across different populations and nonsense mutations are associated with severe phenotypes.
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Prapaporn
authors.initials: P
authors.lastname: Vilaiphan
authors.forename: Pantipa
authors.initials: P
authors.lastname: Chatchatee
authors.forename: Jarungchit
authors.initials: J
authors.lastname: Ngamphaiboon
authors.forename: Siraprapa
authors.initials: S
authors.lastname: Tongkobpetch
authors.forename: Kanya
authors.initials: K
authors.lastname: Suphapeetiporn
authors.forename: Vorasuk
authors.initials: V
authors.lastname: Shotelersuk
mesh_terms: D000328:Adult; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009035:Mothers; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D013785:Thailand
chemical_list: D018389:Codon, Nonsense; D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases