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Kinga M. Bujakowska, Isabelle S. Audo, Saddek Mohand-Saïd, Melanie Letexier, Jean-Paul Saraiva, Christine Lonjou, Wassila Carpentier, José-Alain Sahel, Shomi S. Bhattacharya; Strategies To Identify Genetic Variants In Autosomal Recessive Rod-cone Dystrophy Patients. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4517.
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To genetically investigate simplex and autosomal recessive (ar) rod-cone dystrophy patients in a French cohort and to perform phenotype-genotype correlations.
Patients underwent a full ophthalmic examination. Informed consent was obtained from each patient and unaffected family member. The study protocol adhered to the tenets of the Declaration of Helsinki and was approved by the local ethics committee. The DNA of approximately 400 index patients with a precise diagnosis of simplex and ar rod-cone dystrophy was extracted and genotyped by means of an arRP genotyping microarray, homozygosity mapping using a 700K SNP microarray and next-generation sequencing (NGS) using exome capture of 250 retinal genes.
Eleven unrelated patients with ar or simplex rod-cone dystrophy carried likely pathogenic variants of CRB1 of which seven were novel. Two patterns of fundus pigmentary changes were observed: a typical bone spicule-shaped pigment migration within the peripheral retina and widespread clumped pigmentary changes of nummular appearance at the level of the retinal pigment epithelium. All patients presented with macular involvement. We did not distinguish a clear genotype-phenotype correlation regarding the fundus appearance. Other known genes involved in ar rod-cone dystrophy will be described as reported for CRB1 here.
Given a high rate of novel mutations in known rod-cone dystrophy genes and high cost of exclusion of known genes by direct sequencing, the most efficient method to rapidly screen an uncharacterized cohort is to perform NGS with targeted exome capture for known genes implicated in retinal disorders.
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