Familial retinal detachment associated with COL2A1 exon 2 and FZD4 mutations

Clin Exp Ophthalmol. 2012 Jul;40(5):476-83. doi: 10.1111/j.1442-9071.2012.02804.x. Epub 2012 Jun 19.

Abstract

Background: To characterize the clinical and genetic abnormalities within two Australian pedigrees with high incidences of retinal detachment and visual disability.

Design: Prospective review of two extended Australian pedigrees with high rates of retinal detachment.

Participants: Twenty-two family members from two extended Australian pedigrees with high rates of retinal detachment were examined.

Methods: A full ophthalmic history and examination were performed, and DNA was analysed by linkage analysis and mutation screening.

Main outcome measures: Characterization of a causative hereditary gene mutation in each family.

Results: All affected family members of one pedigree carried a C192A COL2A1 exon 2 mutation. None of the affected family members had early-onset arthritis, hearing abnormalities, abnormal clefting or facial features characteristic of classical Stickler syndrome. All affected members of the familial exudative vitreoretinopathy pedigree carried a 957delG FZD4 mutation.

Conclusions: Patients with retinal detachment and a positive family history should be investigated for heritable conditions associated with retinal detachment such as Stickler syndrome and familial exudative vitreoretinopathy. The absence of non-ocular features of Stickler syndrome should raise the possibility of mutations in exon 2 of COL2A1. Similarly, late-onset familial exudative vitreoretinopathy may appear more like a rhegmatogenous detachment and not be correctly diagnosed. When a causative gene mutation is identified, cascade genetic screening of the family will facilitate genetic counselling and screening of high-risk relatives, allowing targeted management of the pre-detachment changes in affected patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arthritis / diagnosis
  • Arthritis / genetics
  • Collagen Type II / genetics*
  • Connective Tissue Diseases / diagnosis
  • Connective Tissue Diseases / genetics
  • DNA Mutational Analysis
  • Exons / genetics*
  • Female
  • Frizzled Receptors / genetics*
  • Hearing Loss, Sensorineural / diagnosis
  • Hearing Loss, Sensorineural / genetics
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Polymerase Chain Reaction
  • Prospective Studies
  • Retinal Detachment / diagnosis
  • Retinal Detachment / genetics*
  • Visual Acuity / physiology
  • Vitreoretinopathy, Proliferative / diagnosis
  • Vitreoretinopathy, Proliferative / genetics

Substances

  • COL2A1 protein, human
  • Collagen Type II
  • FZD4 protein, human
  • Frizzled Receptors

Supplementary concepts

  • Stickler syndrome, type 1