{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:48:38Z","timestamp":1791359318413,"version":"4.3.1"},"reference-count":45,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T00:00:00Z","timestamp":1745625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Region \u00d6sterg\u00f6tland (ALF), FORSS (Medical Research Council of Southeast Sweden)","award":["FUTURUM-941559"],"award-info":[{"award-number":["FUTURUM-941559"]}]},{"name":"Futurum (the research council of Region J\u00f6nk\u00f6ping)","award":["FUTURUM-941559"],"award-info":[{"award-number":["FUTURUM-941559"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Apical hypertrophic cardiomyopathy (ApHCM) is a distinct variant of hypertrophic cardiomyopathy (HCM). Few studies have focused on the genetic determinants of this subtype. We aimed to investigate the genetic basis of apical hypertrophy in a Swedish cohort. Methods\u2013Results: Longitudinal data on 58 unrelated index patients with ApHCM from the Southeast healthcare region in Sweden from 2010 to 2024 were assessed retrospectively. Additionally, the original raw data from genetic testing were re-evaluated using AI-based Emedgene software. Patients were 47 \u00b1 14 years old, and 60% males. A total of 72.4% had the pure apical type and the remaining had the mixed phenotype, dominant distal. In the cohort, 50\/58 (86.2%) underwent genetic testing, of whom 7\/50 (14%) were considered genotype positive for a pathogenic\/likely pathogenic variant, mainly in MYH7 (43%) and in the non-sarcomeric ALPK3 gene (28.6%). A re-evaluation of the original data from genetic testing identified a previously unreported variant in the skeletal muscle \u03b1-actin (ACTA1) gene. Overall, 21 of 58 patients (36.2%) had HCM-related events during their disease course: 10% had a stroke, and 12% had heart failure. Atrial fibrillation was present in 41.4% and non-sustained ventricular tachycardia occurred in 29.3% of the patients. Apical aneurysm was observed in 17.2% of cases. Patients with a positive genotype were more likely to have a positive family history of HCM compared to those with a negative genotype (p = 0.020). Conclusions: In ApHCM, a positive genotype was found less frequently compared to classic HCM. Only 14% of patients with ApHCM were found to be genotype positive, indicating that apical hypertrophy represents a genetically unique population with low risk of mortality. Nevertheless, patients with ApHCM faced higher rates of atrial fibrillation, ventricular arrhythmias, and apical aneurysms.<\/jats:p>","DOI":"10.3390\/genes16050494","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T11:00:54Z","timestamp":1745924454000},"page":"494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Unravelling the Genotype of the Apical Variant of Hypertrophic Cardiomyopathy in a Swedish Cohort"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8988-5591","authenticated-orcid":false,"given":"Antheia","family":"Kissopoulou","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, County Council of J\u00f6nk\u00f6ping, Department of Health, Medicine and Caring Sciences, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2097-6778","authenticated-orcid":false,"given":"Rada","family":"Elleg\u00e5rd","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, and Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Ingemarsdotter","family":"Fernlund","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, Division of Pediatrics, Link\u00f6ping University, Crown Princess Victoria Children\u2019s Hospital, Link\u00f6ping University Hospital, 58185 Link\u00f6ping, Sweden"},{"name":"Department of Clinical Sciences Lund, Lund University, Skane University Hospital, Pediatric Heart Center, 22185 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2632-4065","authenticated-orcid":false,"given":"Jan-Erik","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, County Council of J\u00f6nk\u00f6ping, Department of Health, Medicine and Caring Sciences, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8015-5728","authenticated-orcid":false,"given":"Henrik","family":"Green","sequence":"additional","affiliation":[{"name":"Division of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"},{"name":"Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, 58185 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Gunnarsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, and Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"},{"name":"Centre for Rare Diseases in South East Region of Sweden, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1536\/ihj.17.611","article-title":"Giant T wave inversion as a manifestation of asymmetrical apical hypertrophy (AAH) of the left ventricle. 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