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Delivering it: Stargardt disease
Author(s) -
NEMETH AH,
DOWNES S
Publication year - 2012
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2012.2663.x
Subject(s) - abca4 , stargardt disease , sanger sequencing , retinitis pigmentosa , dna sequencing , retinal degeneration , genetic testing , medicine , bioinformatics , macular degeneration , genetics , biology , computational biology , ophthalmology , gene , phenotype
Purpose To investigate the use of Sanger and Next Generation Sequencing (NGS) in patients with Stargardt Disease and other ABCA4 retinopathies Methods Comparison of NGS with traditional Sanger sequencing in patients with possible ABCA4 retinopathies and the development of a clinical diagnostics service for inherited retinal degeneration using NGS. Results When ABCA4 was tested using Sanger sequencing, the mutation detection rate in patients with a clinical diagnosis of STGD disease was ~80%. In patients with other phenotypes compatible with ABCA4 mutations (eg. end‐stage chorioretinal atrophy, Bulls eye maculopathy or Pattern dystrophy) the detection rate was lower but still significant. Evaluation of NGS using ABCA4 as a test system showed that this technology, particularly the Illumina platform, was highly reliable in detecting the mutations found using Sanger sequencing. When NGS was used in a group of patients with Retinitis Pigmentosa or Cone‐Rod Dystrophy, ~ 6% were found to have ABCA4 mutations, illustrating the heterogeneous phenotype of ABCA4 retinopathies and the difficulties in making a clinical diagnosis. Conclusion Sequencing is the most efficient method of detecting mutations in STGD and will replace screening technologies. Genetic testing in STGD allows clinicians to improve their clinical pattern recognition, facilitate genetic counselling and identify patients for clinical trials. NGS compared to Sanger sequencing has the added advantage that numerous other genes can be sequenced at the same time and is reliable and cost effective, thereby providing an invaluable diagnostic tool. Genetic testing using NGS for genes involved in retinal degeneration is now available as a service through the Oxford laboratory (www.ouh.nhs.uk/geneticslab).