Abstract
Purpose
Inherited cataract, opacification of the lens, is the most common worldwide cause of blindness in children. We aimed to identify the genetic cause of isolated autosomal-dominant lamellar cataract in a five-generation British family.
Methods
Whole exome sequencing (WES) was performed on two affected individuals of the family and further validated by direct sequencing in family members.
Results
A novel missense mutation NM_001040667.2:c.190A>G;p.K64E was identified in the DNA-binding-domain of heat-shock transcription factor 4 (HSF4) and found to co-segregate with disease.
Conclusion
We have identified a novel mutation in HSF4 in a large British pedigree causing dominant congenital lamellar cataract. This is the second mutation in this gene found in the British population. This mutation is likely to be dominant negative and affect the DNA-binding affinity of HSF4.
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Acknowledgements
This work was supported by grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust and UCL Institute of Ophthalmology (UK), Moorfields Eye Hospital Special Trustees (UK), Moorfields Eye Charity (UK), and the Foundation Fighting Blindness (USA). MM is supported by an FFB Career Development Award. We thank the members of the family for taking part in this study. We also thank Manav Ponnekanti who helped in the formatting of the document.
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Berry, V., Pontikos, N., Moore, A. et al. A novel missense mutation in HSF4 causes autosomal-dominant congenital lamellar cataract in a British family. Eye 32, 806–812 (2018). https://doi.org/10.1038/eye.2017.268
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DOI: https://doi.org/10.1038/eye.2017.268
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