Novel nonsense mutation in C2orf71 gene in a brazilian patient with autosomal recessive cone-rod dystrophy

Abstract

Purpose: To report a case of a patient with autosomal recessive cone-rod dystrophy (arCRD) with a novel nonsense mutation in the C2orf71 gene, which had never been associated with cone-rod dystrophy before.

Methods: Ocular examination was performed. Best-corrected visual acuity (BCVA) was done using the Snellen chart. Color test was done with Farnsworth D-15 dichromatous color blindness test. Additionally the patient underwent contrast sensitivity test (Reichert Clear Chart 2), stereoacuity test (butterfly stereoacuity test with lea symbols), visual field test using Goldmann semiautomatic kinetic perimetry (Octopus 900, Haag-Streit), and retinography with TRC50DX, Topcon. Genetic testing was done by PCR amplification and bidirectional DNA sequencing of all coding exons and exon/intron boundaries in a CLIA certified laboratory. The results were analyzed and compared to the NCBI reference sequence NM_001029883.2. PSIPRED was used to predict the secondary structure of the protein.

Results: 48-year-old brazilian female born from consanguineous parents, BCVA 20/250 on both eyes, presented central vision and color vision loss initiated at 24 years old, followed in the next years by peripheral visual field loss and progressive nyctalopia. Ophthalmic examination revealed rotational nystagmus, macular atrophy and peripheral bone spicules, mainly inferiorly. Farnsworth D-15 test demonstrated color blindness, specially protanomaly and deuteranomaly, at the contrast sensitivity test only optotypes with at least 25% of contrast could be noted, and no stereopsis was detected. Goldmann semiautomatic kinetic perimetry demonstrated central scotoma and an important peripheral visual field loss, specially superiorly. Sequencing for the C2orf71 gene was performed revealing the novel nonsense mutation c.1837C>T:p.R613X. According to PSIPRED predictions this nonsense mutation disrupts the protein translation at the 11th and last helical structure of the polypeptide chain.

Conclusions: Currently, arCRD is associated with mutations in 22 different genes, not including, up to now, the C2orf71 gene. Additionally, this gene was previously only associated with retinitis pigmentosa, therefore herein we exhibit a situation of phenotype heterogeneity related to the gene C2orf71.

Keywords: 539 genetics • 696 retinal degenerations: hereditary • 695 retinal degenerations: cell biology