A unique triadin exon deletion causing a null phenotype

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Presentation transcript:

A unique triadin exon deletion causing a null phenotype Barry M. O’Callaghan, MRCPCH, Jules C. Hancox, FBPhS, Alan G. Stuart, FRCP, Catherine Armstrong, MRCPCH, Maggie M. Williams, BSc, FRCPath, Alison Hills, PhD, Hazel Pearce, BSc, Carolyn L. Dent, PhD, Mary Gable, BSc, Mark A. Walsh, MRCPCH HeartRhythm Case Reports Volume 4, Issue 11, Pages 514-518 (November 2018) DOI: 10.1016/j.hrcr.2018.07.014 Copyright © 2018 Terms and Conditions

Figure 1 A: Electrocardiogram 6 days post cardiac arrest. There was a prolonged QTc interval of 490 ms and T-wave inversion in the anterior precordial leads from V1 to V5. B: Episode of ventricular fibrillation that was effectively converted by a single shock, 7 months postimplantation. HeartRhythm Case Reports 2018 4, 514-518DOI: (10.1016/j.hrcr.2018.07.014) Copyright © 2018 Terms and Conditions

Figure 2 Quantitative analysis data showing the TRDN homozygous deletion of exon 2 in (1) the index case and heterozygous deletion in (2) both parents. A: Multiplex ligation-dependent probe amplification (MLPA) analysis using control probes targeting exons 1 and 3 in addition to standard control probes included within MLPA kit (P200). (1) The index case shows complete absence of 2 probes targeting different regions of TRDN exon 2. (2) Both parents have patient/reference ratios < 0.61 for both exon 2 probes, indicating a heterozygous deletion. B: Droplet digital polymerase chain reaction (ddPCR) analysis indicating absence of TRDN exon 2 in the index case and reduced signal in the maternal sample confirming heterozygous state. HeartRhythm Case Reports 2018 4, 514-518DOI: (10.1016/j.hrcr.2018.07.014) Copyright © 2018 Terms and Conditions

Figure 3 A, B: Normal functioning of the TRDN gene with the KEKE component close to the C-terminus, which interacts with CASQ2 and RYR2. C: Dashed lines show that components of TRDN missing in our patient, which will result in the inability of the protein to interact with CASQ2 and RYR2, and inability to anchor in the membrane of the sarcoplasmic reticulum (SR).14 HeartRhythm Case Reports 2018 4, 514-518DOI: (10.1016/j.hrcr.2018.07.014) Copyright © 2018 Terms and Conditions