Adult onset X-linked chronic granulomatous disease in a woman patient caused by a de novo mutation in paternal-origin CYBB gene and skewed inactivation of normal maternal X chromosome.
We report a 28-year-old woman patient suffering from refractory subcutaneous abscess. Stimuli-induced microbicidal reactive oxygen metabolites formation test of the patient's neutrophils revealed that only 9.6% of the neutrophils produced H2O2. DNA analysis of the CYBB that encodes gp91(phox) demonstrated that she was heterozygous for a nonsense mutation, 206Trp(TGG)/stop(TGA) and therefore, a diagnosis of adult onset X-linked chronic granulomatous disease was made. Our molecular biological study revealed that her disease was caused by a de novo mutation in the CYBB gene on the paternal-origin X-chromosome and a skewed inactivation of the normal maternal X-chromosome.
Gono
Takahisa
T
Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto.
Yazaki
Masahide
M
Agematsu
Kazunaga
K
Matsuda
Masayuki
M
Yasui
Kozo
K
Yamaura
Maki
M
Hidaka
Fumio
F
Mizukami
Tomoyuki
T
Nunoi
Hiroyuki
H
Kubota
Takeo
T
Ikeda
Shu-Ichi
S
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D018389:Codon, Nonsense; D018388:Codon, Terminator / Q000235:genetics; D004247:DNA / Q000235:genetics; D005260:Female; D050172:Genes, X-Linked; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006105:Granulomatous Disease, Chronic / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics*; D009504:Neutrophils / Q000378:metabolism; D049951:X Chromosome Inactivation
D018389:Codon, Nonsense; D018388:Codon, Terminator; D008562:Membrane Glycoproteins; D004247:DNA; D006861:Hydrogen Peroxide; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases