Leber Congenital Amaurosis: First Genotyped Hungarian Patients and Report of 2 Novel Mutations in the CRB1 and CEP290 Genes

• Published in: European journal of ophthalmology 2016-01, Vol.26 (1), p.78-84
• Main Authors: Vámos, Rita, Külm, Maigi, Szabó, Viktoria, Ahman, Aune, Lesch, Balázs, Schneider, Miklós, Varsányi, Balázs, Nagy, Zoltán Zsolt, Németh, János, Farkas, Ágnes
• Format: Article
• Language: English
• ISSN: 1120-6721; 1724-6016
• DOI: 10.5301/ejo.5000643

Purpose To introduce the first Hungarian patients with genetically defined Leber congenital amaurosis (LCA) and to report 2 novel mutations. Methods Seven otherwise healthy patients (4-29 years, 5 male and 2 female) who had an onset of severe visual impairment before age 2 years were investigated. The diagnosis was established in all individuals by medical history, funduscopy, and full-field electroretinogram (ERG). Ocular examination included visual acuity testing, digital fundus photography, and in 6 patients retinal imaging with optical coherence tomography (OCT). Arrayed primer extension microarray screening was performed in all probands. In 2 patients, further Sanger sequencing and targeted next-generation sequencing revealed the second disease allele. Results A cone-rod type LCA was revealed in 4 patients and a rod-cone type disease in 3 patients. Five patients presented with maculopathy. Optical coherence tomography (OCT) imaging showed diffuse retinal thickening in 3 probands with severe macular atrophy in one. Full-field ERGs were undetectable or residual in all patients. Genetic screening revealed AIPL1, CRB1, and CEP290 gene-related pathology in 6 patients; in 1 proband, no mutation was found. Three homozygous and 3 compound heterozygous mutations were identified. Two novel variants were detected: c.2536G>T (p.G846X) in the CRB1 gene and c.4929delA (p.Lys1643fsX2) in the CEP290 gene. Conclusions Genetic subtypes identified are among the most common ones in LCA; the phenotypes are consistent with those reported previously. Both novel mutations are predicted to result in a premature translation termination. The phenotype related to the novel CRB1 mutation results in severe atrophic maculopathy.