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Birgit Lorenz, Ute Schneider, Hanno J Bolz, Christoph Friedburg, Monika Andrassi-Darida, Markus N Preising; Genotype-Phenotype Correlation in Inherited Retinal Diseases Caused By Biallelic CEP290 Variations. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4515.
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© ARVO (1962-2015); The Authors (2016-present)
Inherited retinal diseases (IRDs) may be caused by variations in genes affecting the connecting cilium of photoreceptor cells and the intraflagellar transport summarized 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.
We performed genotype-phenotype correlations in 29 patients with biallelic mutations in CEP290. The study was approved by the IRB of the medical faculty, JLU Giessen. The patients received a comprehensive clinical examination including spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) recording, and electrophysiology whenever possible.
We compiled data from a median age at first visit of 0.7 y and a median follow-up period of 5.1 y (range 6 m to 25.7 y). The oldest patient was 84 y at last visit.The frequent deep intronic variation c.2991+1655A>G was present in 21 patients (42 / 58 alleles), 6 patients were homozygous. The second most frequent variation was p.K1575* (10 / 58 alleles). None of the patients had signs of syndromic IRD.All patients had electrophysiological responses below threshold and severely reduced visual acuity from birth on. Absent fixation of targets was noted in 15 patients during the first months of life. Six 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). Nine patients had quantifiable BCVA (logMAR 2 – 0.7), in one case up to the age of 84 y. 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 FAF signals in the perimacular ring and in the rod ring, and spotty in the periphery. SD-OCT disclosed reduced photoreceptor layer (OPL to OS) thickness and preserved inner retinal thickness (RNFL to INL). Better BCVA did not correlate to central photoreceptor layer thickness.
As reported earlier CEP290 variations are one of the most frequent causes of IRDs with infancy onset. In our patient cohort of 29 patients, only 34% had no LP, 65% at least LP, and 31% logMAR 2 to 0.7. Together with preserved ganglion cell and nerve fiber cell layers hope for success in therapeutic approaches is given.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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