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

Vamos, R [Vámos, Rita (Szemészet), szerző] Szemészeti Klinika (SE / AOK / K); Kulm, M; Szabo, V [Szabó, Viktória (szemészet), szerző] Szemészeti Klinika (SE / AOK / K); Ahman, A; Lesch, B [Lesch, Balázs (Szemészet), szerző] Szemészeti Klinika (SE / AOK / K); Schneider, M [Schneider, Miklós (Szemészet), szerző] Szemészeti Klinika (SE / AOK / K); Varsanyi, B [Varsányi, Balázs (Szemészet), szerző] Szemészeti Klinika (PTE / ÁOK); Nagy, ZZ [Nagy, Zoltán Zsolt (Szemészet), szerző] Szemészeti Klinika (SE / AOK / K); Nemeth, J [Németh, János Tibor (Szemészet), szerző] Szemészeti Klinika (SE / AOK / K); Farkas, A [Farkas, Ágnes (Szemészet), szerző] Szemészeti Klinika (SE / AOK / K)

Angol nyelvű Tudományos Szakcikk (Folyóiratcikk)
  • SJR Scopus - Medicine (miscellaneous): Q2
    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.
    Hivatkozás stílusok: IEEEACMAPAChicagoHarvardCSLMásolásNyomtatás
    2021-05-12 18:53