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Susanne Kohl, Antje S Bernd, Nicola Gloeckle, Julia Mohr, Eberhart Zrenner, Bernd Wissinger, Saskia Biskup; Genetic testing in patients with inherited retinal dystrophies using panel-based next generation sequencing. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3294.
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© ARVO (1962-2015); The Authors (2016-present)
Inherited retinal dystrophies (RD) constitute a clinically and genetically heterogeneous group of blinding diseases. They can be subdivided according to disease onset, course and progression into i) congenital blindness (i.e. Leber congenital amaurosis), ii) generalized RD with primary peripheral visual loss (i.e. retinitis pigmentosa) or iii) primary central visual loss (i.e. cone and cone-rod dystrophy), iv) macular dystrophies (e.g. Stargardt and Best disease), v) RD with stationary function loss (i.e. congenital stationary nightblindness, achromatopsia), and vi) syndromic forms (e.g. Usher and Bardet-Biedl syndrome), as well as the mode of inheritance. Mutations in more than 100 genes have been described. Consequently, next generation sequencing (NGS) technologies are the most effective approaches to screen and identify mutations in RD.
Over 300 patients with all forms of syndromic and non-syndromic RD were seen at the special day clinic for RD at the Centre for Ophthalmology, University Tuebingen, Germany. Genetic diagnostic testing was performed at CeGaT GmbH by customized panel sequencing on SOLiD 5500xl or HiSeq 2500 Illumina platforms. Currently the platform for RD covers 133 genes subdivided into 9 panels according to clinical diagnosis and most likely mode of inheritance.
Over 450 different mutations and novel variants in 97 different genes were identified. ABCA4, USH2A, EYS and RPGR were the most prevalently mutated genes. In 53.5% of all patients causative mutations were detected, 10.2% of cases were inconclusive and 36.3% remained unsolved. Separated for non-syndromic and syndromic forms, the detection rate is higher with 70.8% for Usher and 69.2% for Bardet-Biedl syndrome. In addition to detection rates, we present prevalences of genes and mutations, as well as novel mutations associated with RD.
Massively parallel panel sequencing is a suitable and effective tool to identify causative mutations in large unselected cohorts of patients affected by all types of RD.
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