Genetic and phenotypic characteristics of three Mainland Chinese families with choroideremia

Mol Vis. 2012:18:309-16. Epub 2012 Feb 3.

Abstract

Purpose: To describe the phenotype and genotype of three Mainland Chinese families affected by choroideremia (CHM).

Methods: Complete ophthalmic examinations were conducted in three unrelated Chinese families with CHM. Peripheral blood samples were collected from the families for genetic and immunoblot analysis. All exons and flanking intronic regions of the gene encoding Rab escort protein-1 (Rep-1) were amplified with PCR and screened for mutations with Sanger sequencing. The three-dimensional structure of mutated Rep-1 was modeled using sequence homology with rat proteins to analyze the effect of the mutation detected in one family.

Results: All affected males had characteristic signs and symptoms of CHM; however, central visual acuity impairment occurred earlier than expected. All female carriers older than 45 years had pigmentary changes, and one female carrier was symptomatic with vision loss. Three different mutations in Rep-1, c.1801-1G>A, c.1130 T>A, and c.612delAG, were detected in the three families.

Conclusions: In Mainland Chinese families, the central visual acuity of male patients with CHM can be affected at an early age (second decade), whereas female CHM carriers may manifest signs and symptoms at a later age (≥ 45 years). One previously reported and two novel Rep-1 mutations were detected in three Chinese patients with CHM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Age of Onset
  • Aged
  • Asian People / genetics
  • Base Sequence
  • China
  • Choroideremia / genetics*
  • Choroideremia / pathology
  • Choroideremia / physiopathology
  • DNA Mutational Analysis
  • Female
  • Fluorescein Angiography
  • Genetic Association Studies
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Models, Molecular
  • Mutation*
  • Pedigree
  • Protein Conformation
  • Visual Acuity / genetics
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • CHM protein, human