Abstract
Abstract 13546: Putative Titin Mutations Associated With Both Long QT Syndrome and Left Ventricular Noncompaction
Circulation (New York, N.Y.), Vol.144(Suppl_1), p.A13546
11/16/2021
DOI: 10.1161/circ.144.suppl_1.13546
Abstract
Introduction:
Inherited long QT Syndrome (LQTS) is characterized by prolonged QTc intervals on electrocardiogram (EKG), ventricular arrhythmias and sudden death (SCD), and is caused by mutations in ion channel or ion-channel related genes. Inherited forms of dilated cardiomyopathy (DCM) and left ventricular noncompaction (LVNC), on the other hand, are caused by mutations in sarcomeric and structural genes including titin.
Methods:
Two unrelated families with histories of SCD presented to us for clinical evaluation of LQTS. Clinical genetic testing covering arrhythmia and cardiomyopathy genes was performed on each proband, with carrier testing on other family members.
Results (Figure):
The proband of family 1 had a strong family history of SCD, carried the clinical diagnosis of LQTS treated with propranolol, and had normal cardiac function by echocardiography. Following chemotherapy with adriamycin for breast cancer, evaluation showed a QTc of 514 ms on EKG, non-sustained VT on Holter, and LVNC with an LVEF=43% on cardiac MRI (cMRI). Genetic testing identified a likely pathogenic nonsense
TTN
variant (p.W18202*) along with a benign
TTN
polymorphism (p.E689K). Her clinically normal daughter did not carry the p.W18202* variant. The proband of family 2 had a strong family history of LQTS and SCD and was diagnosed with LQTS in her 20s after her mother suffered a cardiac arrest. Evaluation showed a QTc of 500 ms on EKG and biventricular LVNC with an LVEF=48% on cMRI. Genetic testing identified a likely pathogenic frameshift
TTN
variant (p.E18038Rfs*47). Three of her children carried the variant and had borderline or prolonged QTc intervals; one had hypertrabeculation on cMRI.
Conclusion:
We have identified two truncating
TTN
variants in close proximity to each other in unrelated families with overlapping LQTS/LVNC/DCM syndromes. Mutations in
TTN
may play a previously unappreciated role in the pathogenesis of inherited arrhythmia syndromes.
Details
- Title: Subtitle
- Abstract 13546: Putative Titin Mutations Associated With Both Long QT Syndrome and Left Ventricular Noncompaction
- Creators
- Alexander M Greiner - The Univ of Iowa, Iowa City, IAMargaret Freese - University of IowaGabriel Kringlen - Internal Medicine, The Univ of Iowa, Iowa City, IAEdward M Powers - Internal Medicine, The Univ of Iowa, Iowa City, IARebecca A Gutmann - UNIVERSITY OF IOWA, Iowa City, IABarry London - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Circulation (New York, N.Y.), Vol.144(Suppl_1), p.A13546
- DOI
- 10.1161/circ.144.suppl_1.13546
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 11/16/2021
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984303004402771
Metrics
1 Record Views