Abstract
Cone and cone-rod dystrophies (CD and CRD, respectively) are degenerative retinal diseases that predominantly affect the cone photoreceptors. The underlying disease gene is not known in approximately 75% of autosomal recessive cases. Variants in NMNAT1 cause a severe, early-onset retinal dystrophy called Leber congenital amaurosis (LCA). We report two patients where clinical phenotyping indicated diagnoses of CD and CRD, respectively. NMNAT1 variants were identified, with Case 1 showing an extremely rare homozygous variant c.[271G > A] p.(Glu91Lys) and Case 2 compound heterozygous variants c.[53 A > G];[769G > A] p.(Asn18Ser);(Glu257Lys). The detailed variant analysis, in combination with the observation of an associated macular atrophy phenotype, indicated that these variants were disease-causing. This report demonstrates that the variants in NMNAT1 may cause CD or CRD associated with macular atrophy. Genetic investigations of the patients with CD or CRD should include NMNAT1 in the genes examined.
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Acknowledgements
We would like to thank the families for their willingness to participate in this study. This study was supported by the National Health and Medical Research Council of Australia (NHMRC Grant: 1099165 to R.V.J. and J.R.G.) and the Costco Organisation.
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Benjamin M. Nash and Richard Symes contributed equally to this work.
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Nash, B.M., Symes, R., Goel, H. et al. NMNAT1 variants cause cone and cone-rod dystrophy. Eur J Hum Genet 26, 428–433 (2018). https://doi.org/10.1038/s41431-017-0029-7
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DOI: https://doi.org/10.1038/s41431-017-0029-7
