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June 27, 2026GenomicsOpen Access

Higher-grade pathogenic variants in obstructive HCM are linked to severe histopathological damage and earlier diagnosis.

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Why the study?

Does variant pathogenicity correlate with histopathological damage and clinical severity in patients with obstructive hypertrophic cardiomyopathy?

Population

193 Chinese Obstructive Hypertrophic Cardiomyopathy patients, median age at operation 40.2 years, 111 men.

Comparison

Genetic testing using a 93-cardiomyopathy-related… vs Patients with VUS and no variants

Design

Cohort

Key result

Higher-grade pathogenic variants in obstructive hypertrophic cardiomyopathy were associated with more severe histopathological damage, earlier diagnosis, and pronounced clinical and rhythm alterations.

Authors

KYKunlun YinYSYang SunHZHuazheng Zhao

Discussion

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Overview

Supports targeted genetic testing in HOCM with sudden death family history; leaves open histopathology's mediating role in genotype-phenotype links.

Key Points

  • This study aims to investigate the relationship between genotype and histopathology in obstructive hypertrophic cardiomyopathy (HOCM), focusing on how these factors influence clinical outcomes.
  • Screened 193 HOCM patients using a 93-gene panel to identify genetic variants.
  • Classified variants as Pathogenic, Likely Pathogenic, or variants of unknown significance (VUS).
  • Evaluated histopathological alterations using septal tissue sections with staining techniques.
  • Patients with LP/P and VUS-LP variants exhibited earlier diagnosis and more severe clinical phenotypes.
  • Association of pathogenic variants with prolonged QRS duration and elevated NT-proBNP levels was observed.
  • Histopathological severity served as a useful metric for evaluating uncertain significance variants.

Study Design

Type

Cohort (n=193)

Structured PICO

Does variant pathogenicity correlate with histopathological damage and clinical severity in patients with obstructive hypertrophic cardiomyopathy?

P
Population
193 Chinese patients with obstructive hypertrophic cardiomyopathy (median age 40.2 years, 42.5% female) evaluated for genotype-histology-phenotype correlations.
E
Exposure
Genetic testing using a 93-cardiomyopathy-related-gene panel (variants classified as Pathogenic, Likely Pathogenic, VUS, VUS-LP)
C
Comparator
Patients with VUS and no variants
O
Outcome
Genotype-phenotype correlations and histopathological alterations (evaluated using 172 septal tissue sections)surrogate

Higher-grade pathogenic variants in HOCM are associated with more severe histopathological changes, earlier diagnosis, and pronounced clinical alterations, highlighting a genotype-histology-phenotype interplay.

Cite This Study

Yin et al. (2026) conducted a cohort in Obstructive Hypertrophic Cardiomyopathy (HOCM) (n=193). Pathogenic, likely pathogenic, or VUS-LP genetic variants vs. Variants of unknown significance (VUS) or no variants was evaluated on Clinical phenotype severity and histopathological alterations. Higher-grade pathogenic variants in obstructive hypertrophic cardiomyopathy were associated with more severe histopathological damage, earlier diagnosis, and pronounced clinical and rhythm alterations.

synapsesocial.com/papers/6a3f9785125782b61d865743https://doi.org/10.1016/j.ygeno.2026.111286
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