Diagnostic Yield of Whole Exome Sequencing in Pediatric Dilated Cardiomyopathy
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Subjects
2.2. WES and Bioinformatics Analysis
2.3. Transmission Electron Microscopy
3. Results
3.1. WES Uncovers De Novo Mutations as a Cause for Early-Onset DCM
3.2. Recurrent LMNA Mutation Associated with Nuclear Inclusions
4. Discussion
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Family | Gene Symbol | Inheritance | Transcript Variant | Protein Variant | CADD or pLI Score (%ile) | ExAC MAF (Eur) | Gene Ontology |
---|---|---|---|---|---|---|---|
DC-82 * | TAF1A | CH | c.251T>C c.1021G>A NM_005681.3 | p.L84S p.G341R | 27.2 (85) 34.0 (99) | 0.007% 0.004% | rRNA transcription |
DC-86 * | ALMS1 | CH | c.4156dupA c.6436C>T NM_015120.4 | p.T1386fs*15 p.R2146* | pLI = n/a | 0.001% 0.001% | Formation/maintenance of primary cilia |
DC-87 * | TNNT2 | De novo | c.421C>T NM_001001430.2 | p.R141W | 33.0 (>95) | -- | Sarcomeric force generation |
DC-90 | LMNA | De novo | c.868G>A NM_170707.3 | p.E290K | 35.0 (>99) | -- | Nuclear lamina |
DC-92 | RBM20 | Presumed de novo | c.1913C>T NM_001134363.2 | p.P638L | 28.0 (90) | -- | Spliceosome |
DC-94 * | RRAGC | De novo | c.224C>A NM_022157.3 | p.S75Y | 27.2 (85) | -- | mTORC1 activation |
DC-95 | TNNT2 | De novo | c.392G>A NM_001001430.2 | p.R131Q | 33.0 (>95) | -- | Sarcomeric force generation |
DC-97 | PRDM16 | De novo | c.1047dupC NM_022114.3 | p.S350fs*48 | pLI = 1.00 (100) | -- | Transcriptional regulation |
DC-101 | LMNA | De novo | c.868G>A NM_170707.3 | p.E290K | 35.0 (>99) | -- | Nuclear lamina |
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Long, P.A.; Evans, J.M.; Olson, T.M. Diagnostic Yield of Whole Exome Sequencing in Pediatric Dilated Cardiomyopathy. J. Cardiovasc. Dev. Dis. 2017, 4, 11. https://doi.org/10.3390/jcdd4030011
Long PA, Evans JM, Olson TM. Diagnostic Yield of Whole Exome Sequencing in Pediatric Dilated Cardiomyopathy. Journal of Cardiovascular Development and Disease. 2017; 4(3):11. https://doi.org/10.3390/jcdd4030011
Chicago/Turabian StyleLong, Pamela A., Jared M. Evans, and Timothy M. Olson. 2017. "Diagnostic Yield of Whole Exome Sequencing in Pediatric Dilated Cardiomyopathy" Journal of Cardiovascular Development and Disease 4, no. 3: 11. https://doi.org/10.3390/jcdd4030011
APA StyleLong, P. A., Evans, J. M., & Olson, T. M. (2017). Diagnostic Yield of Whole Exome Sequencing in Pediatric Dilated Cardiomyopathy. Journal of Cardiovascular Development and Disease, 4(3), 11. https://doi.org/10.3390/jcdd4030011