Original articlePersonalized Diagnosis and Management of Congenital Cataract by Next-Generation Sequencing
Section snippets
Recruitment and Selection of Patients with Congenital Cataract
Patients with CC were diagnosed through the National Health Service (NHS) ophthalmic genetics clinic at Saint Mary's Hospital (Manchester). A 3-generation family history and a full medical history were obtained from all patients, and all patients underwent a detailed ophthalmic examination. Where additional problems or dysmorphic features were present, a full systemic and dysmorphic assessment was undertaken by a clinical geneticist (Table 1, available at www.aaojournal.org). Informed consent
Patient Profiles
The systemic and ophthalmic features of the 36 patients selected for screening are listed in Table 1 (available at www.aaojournal.org), and a selection of cataract morphologies identified during this study are displayed in Figure 1. Analysis of the patient information revealed that 20 patients with nonsyndromic CC and 16 patients with syndromic CC had been selected for testing. It is also noteworthy that 10 of the probands were of consanguineous parentage.
Next-Generation DNA Sequencing Yields Excellent Coverage of Genes Implicated in Human Cataractogenesis
Results from the sequencing of
Discussion
In this study, we used a custom-designed target enrichment for the capture of all coding exons and flanking intronic sequences of genes associated with CC for subsequent massively parallel sequencing. We tested 36 patients and have shown a high mutation detection rate, proving the efficacy of this method in determining the precise genetic cause of CC and providing further evidence of the utility of NGS in the diagnosis of a genetically heterogeneous condition. The absence of previously
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Supplemental material is available at www.aaojournal.org.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Funded by Fight for Sight (grant no. 1831) and supported by the Manchester Academic Health Science Centre and the Manchester National Institute for Health Research Biomedical Research Centre. The funding organization had no role on the design or conduct of this research.