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Autosomal recessive...
Autosomal recessive cardiomyopathy and sudden cardiac death associated with variants in MYL3
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- Osborn, D. P. S. (author)
- Genetics Research Centre, Molecular and Clinical Sciences Institute, St George’s University of London, United Kingdom
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- Emrahi, L. (author)
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University Tehran, Iran
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- Clayton, J. (author)
- Centre for Medical Research, The University of Western Australia and the Harry Perkins Institute of Medical Research, Nedlands, WA, Australia
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- Tabrizi, M. T. (author)
- Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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- Wan, A. Y. B. (author)
- Genetics Research Centre, Molecular and Clinical Sciences Institute, St George’s University of London, United Kingdom
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- Maroofian, R. (author)
- Genetics Research Centre, Molecular and Clinical Sciences Institute, St George’s University of London, United Kingdom
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- Yazdchi, M. (author)
- Centre for Neuroscience Research center, Tabriz University of medical science, Tabriz, Iran
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- Garcia, M. L. E. (author)
- Genetics Research Centre, Molecular and Clinical Sciences Institute, St George’s University of London, United Kingdom
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- Galehdari, H. (author)
- Department of Genetics, Faculty of Science, Shahid Chamran University of Ahvaz, Iran
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- Hesse, Camilla (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine,Institute of Biomedicine, Sahlgrenska academy, University of Gothenburg, Sweden
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- Shariati, G. (author)
- Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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- Mazaheri, N. (author)
- Department of Genetics, Faculty of Science, Shahid Chamran University of Ahvaz, Iran
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- Sedaghat, A. (author)
- Health Research Institute, Diabetes Research Center, Ahvaz Jundishapur University of medical Sciences, Ahvaz, Iran
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- Goullee, H. (author)
- Centre for Medical Research, The University of Western Australia and the Harry Perkins Institute of Medical Research, Nedlands, WA, Australia
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- Laing, N. (author)
- Centre for Medical Research, The University of Western Australia and the Harry Perkins Institute of Medical Research, Nedlands, WA, Australia
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- Jamshidi, Y. (author)
- Genetics Research Centre, Molecular and Clinical Sciences Institute, St George’s University of London, United Kingdom
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- Tajsharghi, Homa (author)
- Högskolan i Skövde,Institutionen för hälsovetenskaper,Forskningsmiljön hälsa, hållbarhet och digitalisering,Centre for Medical Research, The University of Western Australia and the Harry Perkins Institute of Medical Research, Nedlands, WA, Australia,Translationell medicin TRIM, Translational Medicine
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- English.
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In: Genetics in Medicine. - : Elsevier BV. - 1098-3600 .- 1530-0366. ; 23:4, s. 787-792
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https://doi.org/10.1...
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Abstract
Subject headings
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- Purpose Variants in genes encoding sarcomeric proteins are the most common cause of inherited cardiomyopathies. However, the underlying genetic cause remains unknown in many cases. We used exome sequencing to reveal the genetic etiology in patients with recessive familial cardiomyopathy. Methods Exome sequencing was carried out in three consanguineous families. Functional assessment of the variants was performed. Results Affected individuals presented with hypertrophic or dilated cardiomyopathy of variable severity from infantile- to early adulthood-onset and sudden cardiac death. We identified a homozygous missense substitution (c.170C>A, p.[Ala57Asp]), a homozygous translation stop codon variant (c.106G>T, p.[Glu36Ter]), and a presumable homozygous essential splice acceptor variant (c.482-1G>A, predicted to result in skipping of exon 5). Morpholino knockdown of the MYL3 orthologue in zebrafish, cmlc1, resulted in compromised cardiac function, which could not be rescued by reintroduction of MYL3 carrying either the nonsense c.106G>T or the missense c.170C>A variants. Minigene assay of the c.482-1G>A variant indicated a splicing defect likely resulting in disruption of the EF-hand Ca2+ binding domains. Conclusions Our data demonstrate that homozygous MYL3 loss-of-function variants can cause of recessive cardiomyopathy and occurrence of sudden cardiac death, most likely due to impaired or loss of myosin essential light chain function.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences (hsv//eng)
Keyword
- essential light-chain
- hypertrophic cardiomyopathy
- myosin
- mutations
- genetics
- genes
- diagnosis
- spectrum
- Genetics & Heredity
- Translationell medicin TRIM
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Osborn, D. P. S.
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Emrahi, L.
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Clayton, J.
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Tabrizi, M. T.
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Wan, A. Y. B.
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Maroofian, R.
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show more...
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Yazdchi, M.
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Garcia, M. L. E.
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Galehdari, H.
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Hesse, Camilla
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Shariati, G.
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Mazaheri, N.
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Sedaghat, A.
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Goullee, H.
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Laing, N.
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Jamshidi, Y.
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Tajsharghi, Homa
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Health Sciences
- Articles in the publication
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Genetics in Medi ...
- By the university
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University of Gothenburg
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University of Skövde