Mutation spectrum of EYS in Spanish patients with autosomal recessive retinitis pigmentosa

Abstract

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterised ultimately by the loss of photoreceptor cells. We have recently identified a new gene(EYS) encoding an ortholog of Drosophila space maker (spam) as a commonly mutated gene in autosomal recessive RP. In the present study, we report the identification of 73 sequence variations in EYS, of which 28 are novel. Of these, 42.9% (12/28) are very likely pathogenic, 17.9% (5/28)are possibly pathogenic, whereas 39.3% (11/28) are SNPs. In addition, we have detected 3 pathogenic changes previously reported in other populations. We are also presenting the characterisation of EYS homologues in different species, and a detailed analysis of the EYS domains, with the identification of an interesting novel feature: a putative coiled-coil domain.Majority of the mutations in the arRP patients have been found within the domain structures of EYS. The minimum observed prevalence of distinct EYS mutations in our group of patients is of 15.9% (15/94), confirming a major involvement of EYS in the pathogenesis of arRP in the Spanish population. Along with the detection of three recurrent mutations in Caucasian population, our hypothesis of EYS being the first prevalent gene in arRP has been reinforced in the present study.

Figure 1

Coiled coil domain prediction in human EYS protein.

Figure 2

Signal peptide and cleavage site consensus sequence prediction in human EYS protein.

Figure 3

EYS mutation distribution along the domain structure of EYS/EYS. 5' UTR and splice site variations are not included in this depiction.

Figure 4

Family segregation of variations identified in the studied arRP families. Below the individuals, genotypes are presented for each change detected to segregate with the RP. For example, p.G2017V/p.G2017V represents homozygous mutants; p.G2017V/+ indicates heterozygous carriers, +/+ indicates individuals carrying two wild-type alleles, whereas p.R1374X/c.6424+1G>T represents individuals presenting both mutations as compound heterozygous. NA means non available DNA sample.

Figure 4

Family segregation of variations identified in the studied arRP families. Below the individuals, genotypes are presented for each change detected to segregate with the RP. For example, p.G2017V/p.G2017V represents homozygous mutants; p.G2017V/+ indicates heterozygous carriers, +/+ indicates individuals carrying two wild-type alleles, whereas p.R1374X/c.6424+1G>T represents individuals presenting both mutations as compound heterozygous. NA means non available DNA sample.