Associations Between Fundus Types and Clinical Manifestations in Patients with RDH12 Gene Mutations

Abstract

To study the associations between RDH12 gene mutations, fundus types, and clinical manifestations. In total, 46 patients with inherited eye diseases caused by RDH12 gene mutations were included in this study. High-throughput chip capture sequencing, Sanger sequencing, and gene panel detection were used to determine that RDH12 was the pathogenic gene. All patients underwent the following detailed ophthalmic examinations: visual acuity, visual field, intraocular pressure, fundus photography, electroretinography, and optical coherence tomography (OCT). Statistical analysis was used to evaluate the clinical phenotype. A total of 32 mutations were identified in 46 patients. The most common mutations were c.437T > A, c.184C > T, and c.524C > T; the corresponding amino acid changes were p.Val146Asp, p.Arg62Ter, and p.Ser175Leu. Of the 46 patients, retinitis pigmentosa (RP) was found in 31 (68.9%); leber congenital amaurosis (LVA) was found in 11 (24.4%); early onset of severe retinal dystrophy (EOSRD) was found in one (2.2%); cone rod dystrophy (CORD) was found in one (2.2%); and Stargardt disease was found in one (2.2%). There was a significant difference in best-corrected visual acuity among patients based on fundus type (p = 0.0124). Linear trend analysis showed that best-corrected visual acuity gradually decreased as the fundus type increased in severity. In addition, there was a significant difference in the incidence of night blindness among patients with different fundus types (p = 0.0429): types I and IV fundi were associated with the highest incidences of night blindness. RDH12 gene mutation can cause serious inherited retinal diseases, which primarily include RP and LCA. Combined with clinical symptoms and fundus types, the progression of the disease can be characterized and used to guide genetic diagnosis and gene therapy.

Keywords: Fundus features; Gene mutation; Leber congenital amaurosis; RDH12; Retinitis pigmentosa.