Next Article in Journal
Silencing of lncRNA AK045490 Promotes Osteoblast Differentiation and Bone Formation via β-Catenin/TCF1/Runx2 Signaling Axis
Previous Article in Journal
Greatwall-Endosulfine: A Molecular Switch that Regulates PP2A/B55 Protein Phosphatase Activity in Dividing and Quiescent Cells
Open AccessArticle

A Novel DES L115F Mutation Identified by Whole Exome Sequencing is Associated with Inherited Cardiac Conduction Disease

1
Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Tao-Yuan 33305, Taiwan
2
Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan 33305, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(24), 6227; https://doi.org/10.3390/ijms20246227
Received: 21 November 2019 / Revised: 3 December 2019 / Accepted: 8 December 2019 / Published: 10 December 2019
(This article belongs to the Section Molecular Genetics and Genomics)
Inherited cardiac conduction disease (CCD) is rare; it is caused by a large number of mutations in genes encoding cardiac ion channels and cytoskeletal proteins. Recently, whole-exome sequencing has been successfully used to identify causal mutations for rare monogenic Mendelian diseases. We used trio-based whole-exome sequencing to study a Chinese family with multiple family members affected by CCD, and identified a heterozygous missense mutation (c.343C>T, p.Leu115Phe) in the desmin (DES) gene as the most likely candidate causal mutation for the development of CCD in this family. The mutation is novel and is predicted to affect the conformation of the coiled-coil rod domain of DES according to structural model prediction. Its pathogenicity in desmin protein aggregation was further confirmed by expressing the mutation, both in a cellular model and a CRISPR/CAS9 knock-in mouse model. In conclusion, our results suggest that whole-exome sequencing is a feasible approach to identify candidate genes underlying inherited conduction diseases. View Full-Text
Keywords: cardiac conduction disease; exome sequencing; desmin cardiac conduction disease; exome sequencing; desmin
Show Figures

Figure 1

MDPI and ACS Style

Hsu, L.-A.; Ko, Y.-S.; Yeh, Y.-H.; Chang, C.-J.; Chan, Y.-H.; Kuo, C.-T.; Tsai, H.-Y.; Chang, G.-J. A Novel DES L115F Mutation Identified by Whole Exome Sequencing is Associated with Inherited Cardiac Conduction Disease. Int. J. Mol. Sci. 2019, 20, 6227.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop