Identification of mutations in seven Chinese patients with X-linked chronic granulomatous disease

Blood. 1996 Nov 15;88(10):4021-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • China / ethnology
  • DNA Mutational Analysis
  • DNA, Complementary / genetics
  • Exons / genetics
  • Female
  • Frameshift Mutation
  • Granulomatous Disease, Chronic / ethnology
  • Granulomatous Disease, Chronic / genetics*
  • Hong Kong / epidemiology
  • Humans
  • Male
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics*
  • Molecular Sequence Data
  • Mutation*
  • NADPH Oxidase 2
  • NADPH Oxidases / deficiency
  • Point Mutation
  • Polymorphism, Single-Stranded Conformational
  • Protein Structure, Secondary
  • RNA Splicing
  • RNA, Messenger / genetics
  • Sequence Deletion
  • X Chromosome / genetics*

Substances

  • DNA, Complementary
  • Membrane Glycoproteins
  • RNA, Messenger
  • CYBB protein, human
  • NADPH Oxidase 2
  • NADPH Oxidases