The genetic profile of Leber congenital amaurosis in an Australian cohort

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Author
Thompson, JA; De Roach, JN; McLaren, TL; Montgomery, HE; Hoffmann, LH; Campbell, IR; Chen, FK; Mackey, DA; Lamey, TMDate
2017-11-01Source Title
Molecular Genetics and Genomic MedicinePublisher
WILEYUniversity of Melbourne Author/s
Mackey, DavidAffiliation
Ophthalmology (Eye & Ear Hospital)Metadata
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Journal ArticleCitations
Thompson, J. A., De Roach, J. N., McLaren, T. L., Montgomery, H. E., Hoffmann, L. H., Campbell, I. R., Chen, F. K., Mackey, D. A. & Lamey, T. M. (2017). The genetic profile of Leber congenital amaurosis in an Australian cohort. MOLECULAR GENETICS & GENOMIC MEDICINE, 5 (6), pp.652-667. https://doi.org/10.1002/mgg3.321.Access Status
Open AccessDOI
10.1002/mgg3.321Abstract
BACKGROUND: Leber congenital amaurosis (LCA) is a severe visual impairment responsible for infantile blindness, representing ~5% of all inherited retinal dystrophies. LCA encompasses a group of heterogeneous disorders, with 24 genes currently implicated in pathogenesis. Such clinical and genetic heterogeneity poses great challenges for treatment, with personalized therapies anticipated to be the best treatment candidates. Unraveling the individual genetic etiology of disease is a prerequisite for personalized therapies, and could identify potential treatment candidates, inform patient management, and discriminate syndromic forms of disease. METHODS: We have genetically analyzed 45 affected and 82 unaffected individuals from 34 unrelated LCA pedigrees using predominantly next-generation sequencing and Array CGH technology. RESULTS: We present the molecular findings for an Australian LCA cohort, sourced from the Australian Inherited Retinal Disease Registry & DNA Bank. CEP290 and GUCY2D mutations, each represent 19% of unrelated LCA cases, followed by NMNAT1 (12%). Genetic subtypes were consistent with other reports, and were resolved in 90% of this cohort. CONCLUSION: The high resolution rate achieved, equivalent to recent findings using whole exome/genome sequencing, reflects the progression from hypothesis (LCA Panel) to non-hypothesis (RD Panel) testing and, coupled with Array CGH analysis, is a highly effective first-tier test for LCA.
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