ATM gene variants in patients with idiopathic perifoveal telangiectasia

Invest Ophthalmol Vis Sci. 2008 Sep;49(9):3806-11. doi: 10.1167/iovs.07-1357. Epub 2008 May 23.

Abstract

Purpose: To investigate the prevalence of sequence variants in the ATM gene and to determine the frequency of major age-related macular degeneration (AMD)-associated variants in CFH, CFB, and 10q26 loci in patients with idiopathic perifoveal telangiectasia (IPT).

Methods: Thirty patients with diagnoses of IPT underwent standard ophthalmologic evaluation that included visual acuity testing, fundus photography, and fluorescein angiography. DNA was screened for variations in the ATM gene by a combination of denaturing high-performance liquid chromatography and direct sequencing. Major AMD-associated alleles in CFH, CFB, and 10q loci were screened by PCR-restriction fragment-length polymorphism.

Results: Nineteen female and 11 male patients (average age, 59 years) with a median visual acuity of 20/50 were evaluated. Six patients were of Asian-Indian origin, one was Hispanic, and 23 were of European-American ancestry. Nine of 30 (30%) patients had diabetes mellitus, 18 of 30 (60%) patients had hypertension, and 12 of 30 (40%) patients had a history of smoking. Screening of the ATM gene revealed a null allele in 2 of 23 (8.7%) patients of European ancestry, previously disease-associated missense alleles in 4 of 23 (17.4%) patients, and common missense alleles in 7 of 23 (30.4%) patients. No variants were identified in the ATM gene in patients of Asian or Hispanic origin. Frequencies of major AMD-associated alleles in CFH, CFB, and 10q loci in the IPT cohort were similar to those in the ethnically matched general population.

Conclusions: At least 26%, and maybe up to 57%, of IPT patients of European-American descent carried possibly disease-associated ATM alleles. Vascular risk factors such as hypertension, diabetes, and smoking may be associated with the pathogenesis of the disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Ataxia Telangiectasia / diagnostic imaging
  • Ataxia Telangiectasia / genetics*
  • Ataxia Telangiectasia / pathology
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Fovea Centralis / diagnostic imaging
  • Fovea Centralis / pathology
  • Genetic Variation*
  • Humans
  • Macula Lutea / diagnostic imaging
  • Macula Lutea / pathology
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Protein Serine-Threonine Kinases / genetics*
  • Radiography
  • Tumor Suppressor Proteins / genetics*
  • Visual Acuity

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases