Genomic Architecture and Cascade Screening Gaps in Hypertrophic Cardiomyopathy: A Real-World Analysis

Kato, Kaho; Ishikawa, Aki; Mariya, Tasuku; Kouzu, Hidemichi; Yano, Toshiyuki; Kawaharata, Wataru; Takasu, Yuko; Miura, Ayana; Seto, Aiko; Suda, Kentaro; Sakurai, Akihiro

doi:10.3390/jcm15114186

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Open AccessArticle

Genomic Architecture and Cascade Screening Gaps in Hypertrophic Cardiomyopathy: A Real-World Analysis

by

Kaho Kato

¹,

Aki Ishikawa

^1,*

,

Tasuku Mariya

^1,2,*,

Hidemichi Kouzu

³

,

Toshiyuki Yano

³

,

Wataru Kawaharata

³,

Yuko Takasu

¹,

Ayana Miura

¹,

Aiko Seto

¹,

Kentaro Suda

¹ and

Akihiro Sakurai

¹

Division of Genomic and Preventive Medicine, Department of Clinical Genomics, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan

²

Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo 060-0812, Japan

³

Division of Cardiovascular-Kidney-Metabolic Medicine, Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-0812, Japan

^*

Authors to whom correspondence should be addressed.

J. Clin. Med. 2026, 15(11), 4186; https://doi.org/10.3390/jcm15114186

Submission received: 14 March 2026 / Revised: 19 May 2026 / Accepted: 24 May 2026 / Published: 28 May 2026

(This article belongs to the Section Cardiology)

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Abstract

Background/Objectives: Hypertrophic cardiomyopathy (HCM) is genetically heterogeneous, involving more than 11 genes. Since HCM genetic testing was covered by Japan’s national health insurance in 2022, variant detection and the need for family-based intervention have increased, although funding is limited to symptomatic patients only. In this study, we evaluated institutional genetic testing outcomes, factors associated with pathogenic variants, and follow-up of at-risk relatives. Methods: We retrospectively analyzed individuals with confirmed or suspected HCM who underwent genetic testing between October 2022 and June 2025. Data regarding molecular results, family history of cardiomyopathy or sudden cardiac death in first-, second-, and third-degree relatives, and cascade screening were collected. Statistical analysis was performed using R version 2025.09.2 + 418. Results: Among 33 probands (median age, 54 years; 51% male), 13 individuals (39%) had pathogenic or likely pathogenic variants (PV or LPV), while six (18%) harbored variants of uncertain significance (VUS), and 14 (43%) yielded negative results. The PV or LPV cohort was significantly younger at the time of testing (median, 34 vs. 59 years; p = 0.008) and had a family history of PV or LPV (77% vs. 20%; p = 0.005). Only three relatives from two PV or LPV probands underwent cascade genetic screening; two tested positive and initiated targeted cardiac surveillance. Conclusions: Despite achieving actionable results, the restricted uptake of cascade screening highlights the need for improved communication and systemic support to facilitate family-based testing and precision medicine.

Keywords: hypertrophic cardiomyopathy; genetic testing; cascade screening

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MDPI and ACS Style

Kato, K.; Ishikawa, A.; Mariya, T.; Kouzu, H.; Yano, T.; Kawaharata, W.; Takasu, Y.; Miura, A.; Seto, A.; Suda, K.; et al. Genomic Architecture and Cascade Screening Gaps in Hypertrophic Cardiomyopathy: A Real-World Analysis. J. Clin. Med. 2026, 15, 4186. https://doi.org/10.3390/jcm15114186

AMA Style

Kato K, Ishikawa A, Mariya T, Kouzu H, Yano T, Kawaharata W, Takasu Y, Miura A, Seto A, Suda K, et al. Genomic Architecture and Cascade Screening Gaps in Hypertrophic Cardiomyopathy: A Real-World Analysis. Journal of Clinical Medicine. 2026; 15(11):4186. https://doi.org/10.3390/jcm15114186

Chicago/Turabian Style

Kato, Kaho, Aki Ishikawa, Tasuku Mariya, Hidemichi Kouzu, Toshiyuki Yano, Wataru Kawaharata, Yuko Takasu, Ayana Miura, Aiko Seto, Kentaro Suda, and et al. 2026. "Genomic Architecture and Cascade Screening Gaps in Hypertrophic Cardiomyopathy: A Real-World Analysis" Journal of Clinical Medicine 15, no. 11: 4186. https://doi.org/10.3390/jcm15114186

APA Style

Kato, K., Ishikawa, A., Mariya, T., Kouzu, H., Yano, T., Kawaharata, W., Takasu, Y., Miura, A., Seto, A., Suda, K., & Sakurai, A. (2026). Genomic Architecture and Cascade Screening Gaps in Hypertrophic Cardiomyopathy: A Real-World Analysis. Journal of Clinical Medicine, 15(11), 4186. https://doi.org/10.3390/jcm15114186

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Genomic Architecture and Cascade Screening Gaps in Hypertrophic Cardiomyopathy: A Real-World Analysis

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