Leber congenital amaurosis: First genotyped Hungarian patients and report of 2 novel mutations in the CRB1 and CEP290 genes

Rita Vámos, Maigi Külm, Viktoria Szabó, Aune Ahman, Balázs Lesch, Miklós Schneider, Balázs Varsányi, Zoltán Zsolt Nagy, J. Németh, A. Farkas

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)78-84
Number of pages7
JournalEuropean Journal of Ophthalmology
Volume26
Issue number1
DOIs
Publication statusPublished - Jul 2 2015

Keywords

  • AIPL1
  • CEP290
  • CRB1
  • Novel mutations

ASJC Scopus subject areas

  • Ophthalmology

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