Pilot Study of Patients Affected With Leber Congenital Amaurosis (LCA) Clinically Selected With Regard to the Previously Established Genotype–Phenotype Correlations

Abstract

Purpose: : To evaluate the improvement of the genotyping of new patients affected with LCA after pre–selection of genes to study in priority with regard to the genotype–phenotype correlations previously established for the eight hitherto identified genes.

Methods: : This pilot study focused on the two major LCA genes: GUCY2D and CRB1 in 39 unrelated patients selected on their clinical history and ophthalmologic findings: 18/39 suggested the involvement of GUCY2D and 21/39 suggested the implication of CRB1. In each group of patients, the selected gene only was screened for mutations using DHPLC and direct sequencing.

Results: : Ten out of the 18 patients compatible with the involvement of GUCY2D were found to carry mutations in this gene i.e. 55.5% vs 22.1% in a non–clinically pre–selected population of LCA patients. Along the same lines, 11/21 patients of the CRB1 subgroup harboured mutations in this gene i.e. 52.4% vs 10.1% in a non–clinically pre–selected population of patients.

Conclusions: : This study emphasizes the absolute necessity to obtain full and detailed clinical findings for all patients affected with LCA. These data must include: i) the natural history of the disease since birth, ii) the early light behaviour of the child, iii) the exact measurement of the refraction, iv) a precise description of the fundus aspect including the existence or the absence of early macular rearrangements, and finally v) the visual acuity and the visual field recordings when possible.

Keywords: candidate gene analysis • gene screening • retinal degenerations: hereditary