Novel dilated cardiomyopathy associated to Calreticulin and Myo7A gene mutation in Usher syndrome
Abstract We report a novel cardiomyopathy associated to Usher syndrome and related to combined mutation of MYO7A and Calreticulin genes. A 37‐year‐old man with deafness and vision impairment because of retinitis pigmentosa since childhood and a MYO7A gene mutation suggesting Usher syndrome, develope...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-06-01
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| Series: | ESC Heart Failure |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ehf2.13260 |
| _version_ | 1797976441968656384 |
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| author | Andrea Frustaci Alessandro De Luca Nicola Galea Romina Verardo Valentina Guida Rosalba Carrozzo Cristina Chimenti Emanuela Frustaci Luigi Sansone Matteo Antonio Russo |
| author_facet | Andrea Frustaci Alessandro De Luca Nicola Galea Romina Verardo Valentina Guida Rosalba Carrozzo Cristina Chimenti Emanuela Frustaci Luigi Sansone Matteo Antonio Russo |
| author_sort | Andrea Frustaci |
| collection | DOAJ |
| description | Abstract We report a novel cardiomyopathy associated to Usher syndrome and related to combined mutation of MYO7A and Calreticulin genes. A 37‐year‐old man with deafness and vision impairment because of retinitis pigmentosa since childhood and a MYO7A gene mutation suggesting Usher syndrome, developed a dilated cardiomyopathy with ventricular tachyarrhythmias and recurrent syncope. At magnetic resonance cardiomyopathy was characterized by left ventricular dilatation with hypo‐contractility and mitral prolapse with valve regurgitation. At left ventricular endomyocardial biopsy, it was documented cardiomyocyte disconnection because of cytoskeletal disorganization of cell‐to‐cell contacts, including intercalated discs, and mitochondrial damage and dysfunction with significant reduction of adenosine triphosphate production in patient cultured fibroblasts. At an extensive analysis by next‐generation‐sequencing of 4183 genes potentially related to the cardiomyopathy a pathogenic mutation of calreticulin was found. The cardiomyopathy appeared to be functionally and electrically stabilized by a combination therapy including carvedilol and amiodarone at a follow‐up of 18 months. |
| first_indexed | 2024-04-11T04:50:55Z |
| format | Article |
| id | doaj.art-5424ca9909b44b2cb49c53b0d9ef5ee9 |
| institution | Directory Open Access Journal |
| issn | 2055-5822 |
| language | English |
| last_indexed | 2024-04-11T04:50:55Z |
| publishDate | 2021-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj.art-5424ca9909b44b2cb49c53b0d9ef5ee92022-12-27T03:53:07ZengWileyESC Heart Failure2055-58222021-06-01832310231510.1002/ehf2.13260Novel dilated cardiomyopathy associated to Calreticulin and Myo7A gene mutation in Usher syndromeAndrea Frustaci0Alessandro De Luca1Nicola Galea2Romina Verardo3Valentina Guida4Rosalba Carrozzo5Cristina Chimenti6Emanuela Frustaci7Luigi Sansone8Matteo Antonio Russo9Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences Sapienza University Viale del Policlinico 155 Rome 00161 ItalyMedical Genetics Division Fondazione IRCSS Casa Sollievo della Sofferenza San Giovanni Rotondo ItalyDepartment of Experimental Medicine Sapienza University Rome ItalyCellular and Molecular Cardiology Lab IRCCS L. Spallanzani Rome ItalyMedical Genetics Division Fondazione IRCSS Casa Sollievo della Sofferenza San Giovanni Rotondo ItalyMolecular Medicine Laboratory, Department of Neuroscience and Neurorehabilitation IRCCS Bambino Gesù Pediatric Hospital Rome ItalyDepartment of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences Sapienza University Viale del Policlinico 155 Rome 00161 ItalyCellular and Molecular Cardiology Lab IRCCS L. Spallanzani Rome ItalyLaboratory of Molecular and Cellular Pathology IRCCS San Raffaele Pisana Rome ItalyMEBIC Consortium San Raffaele Open University and IRCCS San Raffaele Pisana Rome ItalyAbstract We report a novel cardiomyopathy associated to Usher syndrome and related to combined mutation of MYO7A and Calreticulin genes. A 37‐year‐old man with deafness and vision impairment because of retinitis pigmentosa since childhood and a MYO7A gene mutation suggesting Usher syndrome, developed a dilated cardiomyopathy with ventricular tachyarrhythmias and recurrent syncope. At magnetic resonance cardiomyopathy was characterized by left ventricular dilatation with hypo‐contractility and mitral prolapse with valve regurgitation. At left ventricular endomyocardial biopsy, it was documented cardiomyocyte disconnection because of cytoskeletal disorganization of cell‐to‐cell contacts, including intercalated discs, and mitochondrial damage and dysfunction with significant reduction of adenosine triphosphate production in patient cultured fibroblasts. At an extensive analysis by next‐generation‐sequencing of 4183 genes potentially related to the cardiomyopathy a pathogenic mutation of calreticulin was found. The cardiomyopathy appeared to be functionally and electrically stabilized by a combination therapy including carvedilol and amiodarone at a follow‐up of 18 months.https://doi.org/10.1002/ehf2.13260Usher syndromeMYO7ACALRCalreticulinCardiomyocyte disconnection |
| spellingShingle | Andrea Frustaci Alessandro De Luca Nicola Galea Romina Verardo Valentina Guida Rosalba Carrozzo Cristina Chimenti Emanuela Frustaci Luigi Sansone Matteo Antonio Russo Novel dilated cardiomyopathy associated to Calreticulin and Myo7A gene mutation in Usher syndrome ESC Heart Failure Usher syndrome MYO7A CALR Calreticulin Cardiomyocyte disconnection |
| title | Novel dilated cardiomyopathy associated to Calreticulin and Myo7A gene mutation in Usher syndrome |
| title_full | Novel dilated cardiomyopathy associated to Calreticulin and Myo7A gene mutation in Usher syndrome |
| title_fullStr | Novel dilated cardiomyopathy associated to Calreticulin and Myo7A gene mutation in Usher syndrome |
| title_full_unstemmed | Novel dilated cardiomyopathy associated to Calreticulin and Myo7A gene mutation in Usher syndrome |
| title_short | Novel dilated cardiomyopathy associated to Calreticulin and Myo7A gene mutation in Usher syndrome |
| title_sort | novel dilated cardiomyopathy associated to calreticulin and myo7a gene mutation in usher syndrome |
| topic | Usher syndrome MYO7A CALR Calreticulin Cardiomyocyte disconnection |
| url | https://doi.org/10.1002/ehf2.13260 |
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