{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T10:39:41Z","timestamp":1772015981215,"version":"3.50.1"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hypertrophic cardiomyopathy (HCM) is characterized by an increased left ventricular (LV) wall thickness and LV mass. With an estimated prevalence of 1:200\u2013500, HCM is among the most common genetically determined cardiac diseases. Functionally, enhanced tissue stiffness and reduced elasticity, combined with diastolic dysfunction and myocardial fibrosis, can eventually lead to life-threatening arrhythmias and impaired blood flow through the heart chamber. Typical symptoms associated with HCM include atrial fibrillation (AF), syncope, ventricular fibrillation, and cardiac arrest. At the molecular level, various genetic and\/or non-genetic etiologies can lead to HCM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case summary<\/jats:title><jats:p>In this case, we report on a 60-year-old male patient with severe, progressive hypertrophic cardiomyopathy (HCM) in an uncommon and ambivalent setting. Right ventricular (RV) biopsy and multi-phase skeletal scintigraphy diagnosed transthyretin amyloidosis with cardiac involvement. Sanger sequencing of the transthyretin gene revealed a wild-type sequence. Phenotypically, the patient initially presented with syncopal episodes, atrioventricular (AV) block, and atrial fibrillation. Subsequently, bilateral carpal tunnel syndrome and polyneuropathy developed. However, the progressive and early onset of left ventricular hypertrophy did not align with the typical presentation of HCM in the context of ATTR. Therefore, next-generation sequencing (NGS) analysis revealed a rare chromosomal duplication in both cardiac myosin genes, <jats:italic>MYH6<\/jats:italic> and <jats:italic>MYH7<\/jats:italic>. Consequently, two distinct and rare disease entities co-occurred in this patient, both ultimately leading to HCM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>To date, no other case featuring wild-type transthyretin amyloidosis (wtATTR) concurrently with a chromosomal duplication affecting both cardiac myosin heavy chain genes has been reported in the literature. This highlights the extreme rarity of this condition, making it challenging to ascertain the extent to which a presumably mutated hybrid myosin gene construct or the TTR amyloid fibrils contribute to stiffness, tissue fibrosis, and cardiac dysfunction. Ultimately, both effects converged in this case, leading to the same cardiac disease with an exacerbated phenotypical outcome of hypertrophic cardiomyopathy (HCM). While early onset wtATTR is an uncommon clinical finding, another significant clinical condition was identified in this patient, marked by an unusual copy number variation (CNV) in the genes <jats:italic>MYH6<\/jats:italic> and <jats:italic>MYH7<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2025.1462523","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T06:36:57Z","timestamp":1738564617000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Unusual hypertrophic cardiomyopathy: case report of an early onset wild-type ATTR amyloidosis accompanied by a chromosomal duplication involving the MYH6 and MYH7\u00a0gene"],"prefix":"10.3389","volume":"12","author":[{"given":"Jassin","family":"Hamidi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne","family":"Hanel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Dittmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanda Maria","family":"Gerding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huu Phuc","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Klingel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Schulze-Bahr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s12872-021-01927-5","article-title":"Diagnostic yield of genetic testing in a heterogeneous cohort of 1376 HCM patients","volume":"21","author":"Hathaway","year":"2021","journal-title":"BMC Cardiovasc Disord"},{"key":"B2","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1161\/CIRCRESAHA.117.311059","article-title":"Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy","volume":"121","author":"Marian","year":"2017","journal-title":"Circ Res"},{"key":"B3","doi-asserted-by":"publisher","first-page":"E16","DOI":"10.1002\/clc.20520","article-title":"A novel mutation of the beta myosin heavy chain gene responsible for familial hypertrophic cardiomyopathy","volume":"32","author":"Wang","year":"2009","journal-title":"Clin Cardiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/jcm13237166","article-title":"Advances in cardiac imaging and genetic testing for diagnosis and risk stratification in cardiomyopathies: 2024 update","volume":"13","author":"Gasior","year":"2024","journal-title":"J Clin Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s12968-021-00718-3","article-title":"Effect of sarcomere and mitochondria-related mutations on myocardial fibrosis in patients with hypertrophic cardiomyopathy","volume":"23","author":"Chung","year":"2021","journal-title":"J Cardiovasc Magn Reson"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2528","DOI":"10.1002\/ehf2.13961","article-title":"Prevalence, characteristics, and mortality of patients with transthyretin amyloid cardiomyopathy in the Nordic countries","volume":"9","author":"Lauppe","year":"2022","journal-title":"ESC Heart Fail"},{"key":"B7","doi-asserted-by":"publisher","first-page":"59","DOI":"10.5334\/gh.1262","article-title":"World heart federation consensus on transthyretin amyloidosis cardiomyopathy (ATTR-CM)","volume":"18","author":"Brito","year":"2023","journal-title":"Glob Heart"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2641","DOI":"10.1016\/S0140-6736(15)01274-X","article-title":"Systemic amyloidosis","volume":"387","author":"Wechalekar","year":"2016","journal-title":"Lancet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"223","DOI":"10.3109\/03009734.2014.895786","article-title":"Transthyretin-derived amyloidosis: probably a common cause of lumbar spinal stenosis","volume":"119","author":"Westermark","year":"2014","journal-title":"Ups J Med Sci"},{"key":"B10","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1001\/jama.2017.9236","article-title":"Association between ruptured distal Biceps tendon and wild-type transthyretin cardiac amyloidosis","volume":"318","author":"Geller","year":"2017","journal-title":"JAMA"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2872","DOI":"10.1016\/j.jacc.2019.04.003","article-title":"Transthyretin amyloid cardiomyopathy: JACC state-of-the-art review","volume":"73","author":"Ruberg","year":"2019","journal-title":"J Am Coll Cardiol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.jjcc.2022.01.002","article-title":"Incidence, clinical characteristics, and diagnostic approach in transthyretin amyloid cardiomyopathy: the Kumamoto cardiac amyloidosis survey","volume":"80","author":"Takashio","year":"2022","journal-title":"J Cardiol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/gim.2014.205","article-title":"Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity","volume":"17","author":"Alfares","year":"2015","journal-title":"Genet Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"709419","DOI":"10.3389\/fgene.2021.709419","article-title":"Targeted sequencing of 242 clinically important genes in the Russian population from the Ivanovo region","volume":"12","author":"Ramensky","year":"2021","journal-title":"Front Genet"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms17081239","article-title":"A next-generation sequencing approach to identify gene mutations in early- and late-onset hypertrophic cardiomyopathy patients of an Italian cohort","volume":"17","author":"Rubattu","year":"2016","journal-title":"Int J Mol Sci"},{"key":"B16","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1016\/0092-8674(90)90273-H","article-title":"A molecular basis for familial hypertrophic cardiomyopathy: an alpha\/beta cardiac myosin heavy chain hybrid gene","volume":"62","author":"Tanigawa","year":"1990","journal-title":"Cell"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3919","DOI":"10.1002\/ehf2.12986","article-title":"Heart failure from ATTRwt amyloid cardiomyopathy is associated with poor prognosis","volume":"7","author":"Kocher","year":"2020","journal-title":"ESC Heart Fail"},{"key":"B18","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1161\/CIRCULATIONAHA.115.018852","article-title":"Heart failure resulting from age-related cardiac amyloid disease associated with wild-type transthyretin: a prospective, observational cohort study","volume":"133","author":"Connors","year":"2016","journal-title":"Circulation"},{"key":"B19","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/s41436-020-00970-5","article-title":"Characterization of clinically relevant copy-number variants from exomes of patients with inherited heart disease and unexplained sudden cardiac death","volume":"23","author":"Singer","year":"2021","journal-title":"Gen Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e003223","DOI":"10.1161\/CIRCGEN.120.003223","article-title":"Long-read sequence confirmed a large deletion including MYH6 and MYH7 in an infant of atrial septal defect and atrial arrhythmias","volume":"14","author":"Sonoda","year":"2021","journal-title":"Circ Genom Precis Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.hlc.2019.11.019","article-title":"Amyloid cardiomyopathy","volume":"29","author":"Bart","year":"2020","journal-title":"Heart Lung Circ"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1097\/TP.0000000000002240","article-title":"Outcomes after cardiac transplant for wild type transthyretin amyloidosis","volume":"102","author":"Rosenbaum","year":"2018","journal-title":"Transplantation"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e000098","DOI":"10.1161\/JAHA.113.000098","article-title":"Senile systemic amyloidosis: clinical features at presentation and outcome","volume":"2","author":"Pinney","year":"2013","journal-title":"J Am Heart Assoc"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2025.1462523\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T06:36:59Z","timestamp":1738564619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2025.1462523\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,3]]},"references-count":23,"alternative-id":["10.3389\/fcvm.2025.1462523"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2025.1462523","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,3]]},"article-number":"1462523"}}