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A Novel Mutation in the Intron Enhancer of TRERF1 Causes Cone and Cone-Rod Dystrophy
28 Pages Posted: 8 Oct 2018
More...Abstract
Cone and cone-rod dystrophy (CoD and CoRD) are inheritable retinal disorders that result in severe vision impairment. By whole genome-sequencing (WGS) and Sanger sequencing, we identified a novel mutation chr6:42224396 T>C in the TRERF1 gene carried by all 13 affected but not any of 15 unaffected members in a Chinese family suffering from cone and cone-rod dystrophy. The mutation site is located in an intron enhancer region that was conserved in 84 vertebrate species. qRT-PCR indicated that the patients carrying the mutation have an average of 12.3-fold lower in TRERF1 gene expression than the healthy controls in the same family, which causes the 6.0-fold lower expressions of CDKN1A gene in the patients. TRERF1 is known to regulate CDKN1A that has been implicated in retinal dysfunction in previous studies. Thus, this study uncovers a new genetic cause for CoD/CoRD.
Funding Statement: The National Natural Science Foundation of China (81801132 and 31602023) to HZ and HX, respectively.
Declaration of Interests: The authors declare no conflict of interest.
Ethics Approval Statement: This study was approved by the Sun Yat-sen Memorial hospital, Sun Yat-sen University ethics committee, and informed consent was obtained from all studied participants.
Keywords: cone-rod dystrophy; whole genome sequencing; novel mutation; enhancer
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