The Phenotype of Early Onset Severe Retinal Dystrophy (EOSRD) in Patients With Cep290 Mutations

Abstract

Purpose: : To describe the ocular phenotype and olfactory function in patients with mutations in CEP290.

Methods: : DNA samples from 160 probands with Leber congenital amaurosis (LCA) or early onset severe childhood retinal dystrophies were screened with a microarray (Asper-Ophthalmics) for mutations in CEP290 . Direct sequencing was undertaken in those subjects found to have a mutation on one or both alleles in order to establish a genotype . Patients underwent detailed ophthalmological evaluation and olfactory testing (Sensonics).

Results: : CEP290 mutations were identified in 15 probands. 13 subjects were compound heterozygotes and two subjects were homozygous for CEP290 mutations. Six novel variants were identified. The mutations segregated appropriately in the families and were absent from 100 control chromosomes. Fourteen patients had Leber Congenital Amaurosis and one patient had a childhood onset rod-cone dystrophy. The majority of patients were low hypermetropes. Examination revealed pale optic discs, attenuated retinal vessels and a loss of the foveal reflex. One adult patient had minimal, peripheral pigmentary migration. Electrophysiological investigation showed a non recordable ERG or severe rod and cone dysfunction at diagnosis. Eight patients with CEP290 mutations were able to complete clinical olfactory tests and all were noted to have reduced, age-adjusted scores.

Conclusions: : In this study approximately 10% patients with LCA/EOSRD had known mutations in CEP290 reported by the LCA microarray chip. The proportion of patients with mutations in this gene is likely to be greater as full sequencing of the gene was performed in only a minority of subjects. Affected individuals had very poor vision and nystagmus from infancy and showed progressive visual deterioration with age.

Keywords: gene screening