Identification of Two Recurrent Mutations in EYS Present in Autosomal Recessive Retinitis Pigmentosa Patients

Abstract

Purpose: : To identify prevalent mutations in the gene EYS responsible for autosomal recessive retinitis pigmentosa (arRP). Previously, we identified EYS as the first major gene reported for arRP. We reported the identification of 6 independent mutations in 5 unrelated Spanish families. Recently, 2 mutations have been detected as the molecular cause of arRP in Dutch population. As the starting point of our general purpose, we performed the systematic molecular analysis of the reported mutations in Dutch population in Spanish arRP patients.

Methods: : A molecular study was conducted on DNA extracted from 200 probands with typical RP and indications of recessive inheritance. The detection of the mutations p.Pro2238ProfsX18 and p.Tyr3135X was performed by PCR amplification of exons 33 and 43 of EYS, respectively. Subsequently, direct sequence analysis was performed using the ABI3730 automated sequencer.

Results: : Sequence analysis revealed the presence of both mutations in the Spanish arRP cohort. The mutation p.Tyr3135X was identified as a homozygous nonsense mutation in 1 out of the 200 probands. The calculated genotypic prevalence is consequently of 0.5% among the Spanish arRP population. Secondly, the frameshift mutation p.Pro2238ProfsX18 was detected in the heterozygous state in 1 of the isolated patients, for which the second mutation remains to be identified.

Conclusions: : The molecular analysis of p.Pro2238ProfsX18 and p.Tyr3135X mutations in a Spanish cohort of arRP patients has outlined them as recurrent mutations among the Dutch and the Spanish populations. Whereas the nonsense mutation had been detected in 2 unrelated families of Dutch origin, already reminding it as a frequent mutation, the identification of the frameshift pathogenic variant in the Spanish population confirms that both mutations are of special interest regarding the epidemiology and molecular diagnosis of EYS.

Keywords: retinitis • genetics • mutations