Journal article

Publication year: 2019

Pages: 244-252

Journal: Klinische Monatsblätter für Augenheilkunde

Volume number: 236

Issue number: 3

ISSN: 0023-2165

eISSN: 1439-3999

DOI Link: https://doi.org/10.1055/a-0842-3250

Publisher: Georg Thieme Verlag

Abstract: 

Purpose Inherited retinal diseases (IRDs) may be caused by variations in genes affecting the connecting cilium of photoreceptor cells and intraflagellar transport, manifested as ciliopathies. CEP290 is frequently mutated in non-syndromic, but also syndromic IRDs. In preparation for clinical treatment trials, detailed phenotypic work-up including longitudinal follow-up is mandatory.

Methods We performed genotype-phenotype correlations in 30 patients with biallelic mutations in CEP290. The study was approved by the IRB of the medical faculty of the Justus-Liebig University Giessen. The patients received a comprehensive clinical examination, including spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) recording, and electrophysiology whenever possible.

Results Thirty patients aged 1 month to 84 years (median at first visit 0.6 y) were followed between 5 months and 25.7 years (median 4.8 y). Twenty-three of these patients carried the c.2991+1655A>G mutation (30/60 allele 2, 7 homozygous). The second most frequent mutation was p.K1575* (9/60 alleles). The full-field electroretinogram showed residual response in a few patients only. After progression, electrophysiological responses were below threshold in all patients. Severely reduced visual acuity persisted from birth. Eight patients had quantifiable best corrected visual acuity (BCVA, logMAR 2-0.3), in one case up to the age of 84 y. Absent fixation of targets was noted in 15 patients during the first months of life. Ten of these patients did not improve during follow-up past the second year of life. The other patients developed at least light perception (LP, n = 7) or hand movement (HM, n = 3). Better BCVA was not restricted to the c.2991+1655A>G mutation. Fundus photography documented degenerative changes throughout the retina with macular degeneration and circular increased fundus autofluorescence signals (9/30 patients) in the perimacular ring and in the rod ring, and spotty changes in the periphery. SD-OCT (6/30 patients) disclosed reduced photoreceptor layer (OPL to OS) thickness and preserved inner retinal thickness (RNFL to INL). Better BCVA did not correlate to genotype or central photoreceptor layer thickness.

Conclusion As reported earlier, CEP290 variations are one of the most frequent causes of IRDs with infancy onset. In our patient cohort of 30 patients, only 33% had no LP, 67% at least LP, and among these 26% logMAR 2 to 0.3. Together with preserved ganglion cell and nerve fibre cell layers, success with gene therapeutic approaches appears possible.

Harvard Citation style: Preising, M., Schneider, U., Friedburg, C., Gruber, H., Lindner, S. and Lorenz, B. (2019) The Phenotypic Spectrum of Ophthalmic Changes in CEP290 Mutations, Klinische Monatsblätter für Augenheilkunde, 236(3), pp. 244-252. https://doi.org/10.1055/a-0842-3250

APA Citation style: Preising, M., Schneider, U., Friedburg, C., Gruber, H., Lindner, S., & Lorenz, B. (2019). The Phenotypic Spectrum of Ophthalmic Changes in CEP290 Mutations. Klinische Monatsblätter für Augenheilkunde. 236(3), 244-252. https://doi.org/10.1055/a-0842-3250