Purpose: In order to determine genotype-phenotype correlations in Leber congenital amaurosis (LCA), we analyzed the phenotype and genotype of 250 LCA children. We identified a heterozygous CRX mutation in an affected mother and son, and describe the ocular phenotype of the proband from birth through infancy to age 11 years.
Methods: Best-corrected Snellen visual acuities, electroretinograms (ERGs), and Goldmann visual fields were measured, while SSCP and direct sequencing were done for genotyping.
Results: The proband had congenital nystagmus, amaurotic, paradoxical pupils, and arteriolar narrowing, without a pigmentary retinopathy. The child had very poor fixation and wandering nystagmus at age 5 months, but had measurable vision at age 6 years. Snellen visual acuities were 20/900 at that time, and slowly improved to 20/150 by age 11 years. Perimetry revealed 60 degrees fields with the V4e target at ages 9 and 10 years, with a new 20 degrees inferior island to the III4e target. ERGs at 5 and 8 months were non-detectable, while the photopic ERGs at age 10 years and again at 11 years showed measurable cone a- and b-waves. At age 47, the phenotype of the affected mother consisted of hand motion vision, a pigmentary retinopathy, and non-detectable visual fields and ERGs. We identified a heterozygous CRX mutation, A177Delta1bp (529delG), in both affected individuals, which is predicted to cause a frameshift and introduces a premature termination codon at position 186.
Conclusions: We report a CRX genotype with an ocular phenotype that consists of spontaneous, marked visual improvement in the proband from birth to age 11 years, which is unlike the previous six reports of LCA patients with the CRX genotype.