Cone Dystrophy in Patient with HomozygousRP1L1Mutation

Abstract

The purpose of this study was to determine whether an autosomal recessive cone dystrophy was caused by a homozygousRP1L1mutation. A family including one subject affected with cone dystrophy and four unaffected members without evidence of consanguinity underwent detailed ophthalmic evaluations. The ellipsoid and interdigitation zones on the spectral-domain optical coherence tomography images were disorganized in the proband. The proband had a reduced amplitude of cone and flicker full-field electroretinograms (ERGs). Focal macular ERGs and multifocal ERGs were severely reduced in the proband. A homozygousRP1L1mutation (c.3628T>C, p.S1210P) was identified in the proband. Family members who were heterozygous for the p.S1210P mutation had normal visual acuity and normal results of clinical evaluations. To investigate other putative pathogenic variant(s), a next-generation sequencing (NGS) approach was applied to the proband. NGS identified missense changes in the heterozygous state of thePCDH15,RPGRIP1, andGPR98genes. None of these variants cosegregated with the phenotype and were predicted to be benign reinforcing the putative pathogenicity of theRP1L1homozygous mutation. The AO images showed a severe reduction of the cone density in the proband. Our findings indicate that a homozygous p.S1210P exchange in theRP1L1gene can cause cone dystrophy.