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.