Identification of mutations in seven Chinese patients with X-linked chronic granulomatous disease.
X-linked chronic granulomatous disease (CGD) is due to mutations in the gp91phox gene on Xp21.1. Studies in white and Japanese X-linked CGD patients have shown mutations in nearly every exon. We studied the molecular defect of seven Chinese patients with X-linked CGD from six unrelated families. Mutations were located by single-strand conformation polymorphism and then defined by sequence analysis. The mutations were two different amino acid substitutions, a nonsense mutation, an in-frame trinucleotide deletion, a single A insertion causing a frameshift, and a premature stop. Lastly, a rare splice site mutation caused by G to A transition at the terminal nucleotide of exon 3, resulting in the skipping of exon 3, was found. The possible effects of these mutations on protein structure-function or splicing were discussed. Together with previous reports, the A insertion in the run of six As from nucleotide 749 to 754 and the G to A transition at the terminal position of exon 3 may be mutation hotspots of the gp91phox gene. The extreme heterogeneous mutations found in our patients suggest the absence of ethnic group-specific mutation.
Hui
Y F
YF
Department of Paediatrics, University of Hong Kong, Pokfulam, Hong Kong.
Chan
S Y
SY
Lau
Y L
YL
D000595:Amino Acid Sequence; D001483:Base Sequence; D002681:China / Q000208:ethnology; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D006105:Granulomatous Disease, Chronic / Q000208:ethnology / Q000235:genetics*; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017433:Protein Structure, Secondary; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D017384:Sequence Deletion; D014960:X Chromosome / Q000235:genetics*
D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases