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H. P. Scholl, P. Charbel Issa, I. Ebermann, M. Walger, G. Nurnberg, R. Lang-Roth, C. Becker, P. Nurnberg, F. G. Holz, H. J. Bolz; Non-Syndromic Autosomal Recessive Cone-Rod Dystrophy in a Consanguineous Family Carrying a Novel Splice Site Mutation in the MERTK Gene. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3207. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To describe the phenotype of a consanguineous family segregating autosomal recessive cone-rod dystrophy (CORD).
All family members underwent detailed clinical investigation including best-corrected visual acuity, slit lamp examination, stereoscopic funduscopy and digital fundus photography, Goldmann kinetic visual fields, electroretinography, fundus autofluorescence imaging (cSLO, HRA-2, Heidelberg engineering, Heidelberg, Germany), and high-resolution OCT (SOCT, Optopol, Torun, Poland).
CORD in this family was mapped to chromosome 2q13-q14.1. We have identified homozygosity for a novel splice site mutation in the MERTK gene, c.2189+1G>T, resulting in skipping of exon 16 and a consecutive frameshift. Detailed ophthalmological investigation of the six siblings revealed severe CORD in five of them. They all exhibited a very similar phenotype, which was least severe in the youngest sibling (II:1) and most advanced in the oldest (II:6). FAF imaging revealed spotted increased FAF at the posterior pole in II:1 and, to a lesser degree, in II:3. The older siblings showed patches of decreased FAF. SOCT revealed reduced central retinal thickness, disrupted photoreceptor layer and a granular appearance of the RPE layer. Audiological investigation indicated hair cell and vestibular dysfunction in two siblings affected by CORD and in one witout retinal degeneration. Subsequent linkage and mutation analysis revealed a mutation in a non-syndromic hearing loss gene.
Although MERTK is generally considered an RP gene, these data confirm recent reports that extended the phenotypic spectrum to severe CORD (McHenry et al. IOVS 2004;45:1456-1463; Tschernutter et al. BJO 2006;90:718-723). The phenotypic severity of the CORD in the siblings correlated well with age. The FAF and SOCT findings may indicate that in early stages of the disease reduced RPE phagocytosis results in multifocal autofluorescent photoreceptor debris accumulating between the outer retina and the RPE. In later stages, photoreceptor and RPE cell death would occur as observed in the central macula of the affected individuals.
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