Abstract
Abstract 18890: An MYH7 Mutation Causes Inherited Left Ventricular Noncompaction and Sudden Death in a Large Multigenerational Family
Circulation (New York, N.Y.), Vol.130(suppl_2)
11/25/2014
DOI: 10.1161/circ.130.suppl_2.18890
Abstract
Introduction:
Mutations in
MYH7
, encoding the cardiac β-myosin heavy chain, cause hypertrophic (HCM) and dilated cardiomyopathy (DCM). Recently, several mutations in
MYH7
were reported in patients with left ventricular noncompaction (LVNC), a rare cardiomyopathy characterized by increased trabeculation and sudden death (SCD). No large families with inherited LVNC caused by
MYH7
mutations have been reported.
Methods:
We identified a large family with LVNC and SCD (Pedigree). The proband is a 56 yo woman who presented at age 48 with heart failure, LVNC and a depressed ejection fraction (EF) by echocardiogram (TTE) and cardiac MRI (cMR). Medical records and blood samples were obtained from 20 adult family members, 8 clinically affected (6 LVNC; 2 DCM). DNA was isolated (PureGene), clinical genetic testing for known DCM/LVNC genes was performed on the proband’s affected daughter (GeneDx), and the mutation was identified in family members by direct sequencing. ECGs, TTEs, and cMRs were analyzed to determine PR/QRS/QTc intervals and EF; mutation carriers were compared to non-carriers in the family.
Results:
A heterozygous missense mutation in a hydrophobic coil in the myosin head was identified in exon 14 of
MYH7
(c.1400 T>C; p.Ile467Thr). This mutation was present in all 8 affected members, in 1 clinically unaffected obligate carrier, and in 1 symptomatic subject who had not undergone cardiac testing (penetrance ≥ 0.80). Three obligate carriers suffered SCD. Compared to noncarriers, the EF of mutation carriers was decreased (42 ± 13%, n=9, vs. 58 ±3%, n=4; p=0.03), the PR was borderline long (171 ± 33 vs. 149 ± 12 ms, n=10 each; p=0.06) and the QTc was prolonged (428 ± 32 vs. 405 ± 18 ms, n=10 each; p=0.05).
Conclusion:
The Ile467Thr mutation in
MYH7
causes inherited LVNC with high penetrance and SCD in a large family. Future studies are warranted to differentiate the mechanisms leading from this mutation to LVNC as contrasted with those leading from other
MYH7
mutations to HCM and DCM.
Details
- Title: Subtitle
- Abstract 18890: An MYH7 Mutation Causes Inherited Left Ventricular Noncompaction and Sudden Death in a Large Multigenerational Family
- Creators
- Gina M Morgan - Internal Medicine, Univ of Iowa, Iowa City, IARebecca Gutmann - Internal Medicine, Univ of Iowa, Iowa City, IAAnthony J Klappa - Internal Medicine, Univ of Iowa, Iowa City, IAXiaodong Zhu - University of IowaFerhaan Ahmad - University of IowaHaider Mehdi - University of IowaBarry London - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Circulation (New York, N.Y.), Vol.130(suppl_2)
- DOI
- 10.1161/circ.130.suppl_2.18890
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 11/25/2014
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine; Radiology
- Record Identifier
- 9984302997102771
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