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M. Tschernutter, N.H. Waseem, A. Perkins, S.S. Bhattacharya, G.E. Holder, S.A. Jenkins, A.C. Bird, R.R. Ali, A.R. Webster; Detailed Clinical Characteristics of a Family Segregating a Novel Mutation in the Mertk Gene . Invest. Ophthalmol. Vis. Sci. 2005;46(13):537.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Mutations in Mertk, a gene encoding a tyrosine–kinase receptor involved in photoreceptor disc phagocytosis, have been shown to cause retinal degeneration in the RCS rat, and retinitis pigmentosa in a handful of families. Importantly, gene–replacement therapy in the RCS rat has shown retardation of the degeneration. In a program of work to identify patients and families with potentially treatable retinal degenerations, a panel of 157 unrelated probands with simplex and recessive rod–cone dystrophy were screened for mutations in Mertk. Methods: The 19 exons of the Mertk gene were amplified and analysed using DHPLC. Amplimers showing band–shifts were sequenced. Clinical assessment of affected individuals included fluorescein angiography, electrophysiology, Goldmann perimetry, OCT and autofluorescent imaging. Results: A novel homozygous single base pair deletion (2214delT) was identified in three affected siblings of a family. Occurring in exon 17 the transcript would be expected to succumb to NMD. If translated, it would cause premature truncation within the tyrosine–kinase domain. Further sequence variants in other families were identified but deemed unlikely to cause disease. The three affected individuals experienced nyctalopia before the age of 10 years. Visual acuity and peripheral field were relatively preserved until 18 years. Electrophysiology showed significant attenuation of cone and rod ERG amplitudes from an early age (8 years). A central macula lesion was seen in all three affected individuals, which masked choroidal fluorescence on angiography but appeared brightly hyperautofluorescent on SLO imaging. OCT imaging did not demonstrate debris layer. Conclusions: The clinical characterisation of disease due to Mertk is important to allow the interpretation of any future therapies. The specific macular appearance may allow the identification of further patients through ophthalmic screening, and the rate of visual decline might allow preventative intervention. The milder phenotype compared to that previously reported for a patient with a R722X/R844C genotype indicates variable severity of disease due to mutations in this gene
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