A Mild Phenotype Caused by Two Novel Compound Heterozygous Mutations in CEP290

Abstract

CEP290 is a ciliary gene frequently mutated in ciliopathies, resulting in a broad range of phenotypes, ranging from isolated inherited retinal disorders (IRDs) to severe or lethal syndromes with multisystemic involvement. Patients with non-syndromic CEP290-linked disease experience profound and early vision loss due to cone-rod dystrophy, as in Leber congenital amaurosis. In this case report, we describe two novel loss-of-function heterozygous alterations in the CEP290 gene, discovered in a patient suffering from retinitis pigmentosa using massive parallel sequencing of a molecular inversion probes library constructed for 108 genes involved in IRDs. A milder phenotype than expected was found in the individual, which serves to prove that some CEP290-associated disorders may display preserved cone function.

Keywords: CEP290; ciliopathies; retinitis pigmentosa.

Figure 1

Pedigree of the family of affected proband (marked with an arrow). Variants are marked with V; + represents wild type allele.

Figure 2

Splicing variants discovered in the proband. A. Normal transcript probably produced from both wild-type and c.250+2T>C allele. B. Longer transcript due to alternative splice site usage r.250_251ins250+1_250+28, p.(Glu84Glyfs*10). C. Truncated transcript, r.124_245del, p.(Ser42Phefs* 2).

Figure 3

(a) Electroretinogram of the patient. (b) Macular optical coherence tomography and infrared image.

Figure 4

Fundus photographs of the right (a) and left (b) eye.