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Britta Feldhaus, Susanne Kohl, Nicole Weisschuh, Fadi Nasser, Eberhart Zrenner, Ditta Zobor; Leber congenital amaurosis (LCA): Prevalence of mutations in a large German cohort and clinical characterization of the associated phenotype. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1832.
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© ARVO (1962-2015); The Authors (2016-present)
To describe the prevalence of mutations in LCA-associated genes in a large German cohort, and to give detailed clinical information about their phenotype.
Internal databases were screened for 1) patients with clinical diagnosis of LCA and/or 2) patients with mutations in LCA genes, despite clinical diagnosis. Patients with mere clinical diagnosis were invited for genetic testing. Genomic DNA was analyzed either in a diagnostic-genetic setup using a capture panel of 286 syndromic and non-syndromic IRD genes or a research setup analyzing a panel of 108 IRD genes. Clinical data was obtained mainly retrospectively. In some cases patients were invited for a new ophthalmological examination, including psychophysical tests (best corrected visual acuity (BCVA), color vision, visual field), electrophysiology (fullfield and multifocal electroretinography (ERG)), fundus photography, autofluorescence (FAF) and spectral domain optical coherence tomography (SD-OCT) recordings.
109 patients (54 m, 55 f; age 3-76yrs) with mutations in 16 LCA genes were included. Genetic spectrum displayed the following: CEP290 (22%), CRB1 (21%), RPE65 (14%), RDH12 (13%), AIPL1 (6%), TULP1 (6%), IQCB1 (5%), and sporadically LRAT, CABP4, NMNAT1, RPGRIP1, SPATA7, CRX, IFT140, LCA5 and RD3 (altogether accounting for 13%). Most common clinical diagnosis was LCA (52%, 57/109) followed by RP (40%, 44/109), but also other IRDs were seen (CRD 5%, CSNB 2%, CD 1%). Among LCA patients, 50% were caused by CEP290 (29%) and RPE65 (21%), while other genes were much less frequent (CRB1 11%, AIPL1 11%, IQCB1 9%, RDH12 7% and sporadically LRAT, NMNAT1, CRX, RD3, RPGRIP1). In general, the patients showed a severe phenotype. However, there were exceptional cases with BCVA up to 0.8 (Snellen), good maintained visual fields and preserved photoreceptors in SD-OCT.
This is the first study describing a large German LCA cohort, providing insights into the genetic and phenotypic spectrum in Germany. It reveals CEP290 as the most frequently mutated gene. However, LCA is highly heterogenic and shows clinical variability, overlaps with other IRDs exist. For future gene therapy, the affected gene might be more important to look for than the clinical diagnosis.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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