Two New Mutations in RP1L1 Gene in Occult Macular Dystrophy Patients Associated with a Depolarizing Pattern of Focal Macular ERG

Abstract

Purpose: : To determine whether mutations in the RP1-like protein 1 (RP1L1) gene are present in Japanese patients with sporadic occult macular dystrophy (OMD) and to examine the characteristics of focal macular electroretinograms (ERGs) of the genetically identified OMD

Methods: : Two unrelated individuals with OMD underwent detailed ophthalmic clinical evaluations including focal macular ERGs. Mutation screening of the RP1L1 gene were performed by direct sequencing in patients with OMD.

Results: : Two new RP1L1 mutations were identified including one missense mutation (c.3596 C>G in exon 4) in Case 1 and one insertion (c.325 ins T in exon 2) mutation in Case 2. The variant c.3596 C>G in exon 4 resulted in the substitution of cysteine for serine at amino acid position 1199. The serine at position 1199 is well conserved among the RP1L1 family in other species. The c.325 ins T in exon 2 created a frame shift with 28 additional new residues before a premature termination at codon 137 (p.Pro109SerfsX28). These mutations were not present in 100 control alleles. The waveform of focal macular ERGs recorded from OMD patients had a depolarizing pattern, simulating the ERG waveforms observed after the hyperpolarizing bipolar cell (HBC) activity is blocked.

Conclusions: : Not only autosomal dominant but also some cases of sporadic OMD may be caused by RP1L1 mutations in Japanese patients. The waveform of focal macular ERGs elicited from OMD patients with RP1L1 mutations showed a depolarizing pattern. This characteristics is same as reported for the focal macular ERGs of OMD.

Keywords: electroretinography: clinical • mutations • macula/fovea