Abstract
The macula is a unique structure in higher primates, where cone and rod photoreceptors show highest density in the fovea and the surrounding area, respectively. The hereditary macular dystrophies represent a heterozygous group of rare disorders characterized by central visual loss and atrophy of the macula and surrounding retina. Here we report an atypical absence of ON-type bipolar cell response in a Japanese patient with autosomal dominant macular dystrophy (adMD). To identify a causal genetic mutation for the adMD, we performed whole-exome sequencing (WES) on four affected and four-non affected members of the family for three generations, and identified a novel p.C538Y mutation in a post-synaptic gene, LRRTM4. WES analysis revealed seven rare genetic variations in patients. We further referred to our in-house WES data from 1360 families with inherited retinal diseases, and found that only p.C538Y mutation in LRRTM4 was associated with adMD-affected patients. Combinatorial filtration using public database of single-nucleotide polymorphism frequency and genotype–phenotype annotated database identified novel mutation in atypical adMD.
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Acknowledgements
Computation of the whole-exome analysis was partially performed on the NIG supercomputer at ROIS, National Institute of Genetics, Mishima, Japan. This study was supported by a grant to T.I. from the Japan Agency for Medical Research and Development (16ek0109072h0003).
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Kawamura, Y., Suga, A., Fujimaki, T. et al. LRRTM4-C538Y novel gene mutation is associated with hereditary macular degeneration with novel dysfunction of ON-type bipolar cells. J Hum Genet 63, 893–900 (2018). https://doi.org/10.1038/s10038-018-0465-4
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DOI: https://doi.org/10.1038/s10038-018-0465-4
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