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June 3, 2025Vavilov Journal of Genetics and BreedingOpen Access

CRISPR/Cas9 corrects the MYH7 p.Met659Ile variant to generate two normal, pluripotent patient-specific iPSC lines.

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Why the study?

The clinical significance of approximately 40% of genetic variants in inherited cardiovascular diseases is uncertain, requiring new tools such as CRISPR/Cas9-edited iPSCs to clarify pathogenicity.

Population

iPSCs generated from a carrier of the MYH7 p.Met659Ile (c.1977G>A) variant

Comparison

Correction of the single nucleotide substitution with CRISPR/Cas9

Design

In vitro stem cell gene editing and characterization study

Key result

CRISPR/Cas9 correction of the p.Met659Ile variant in MYH7 in patient-specific iPSCs successfully generated two isogenic iPSC lines that maintained pluripotency and a normal karyotype.

Authors

ASA. E. ShulginaСПС. В. ПавловаJMJ. M. Minina

Discussion

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Overview

Enables mechanistic studies of MYH7-related hypertrophic cardiomyopathy in human cardiomyocytes; leaves open any clinical translation.

Structured PICO

P
Population
Patient-specific induced pluripotent stem cells (iPSCs) derived from a 38-year-old Caucasian male with hypertrophic cardiomyopathy carrying the p.Met659Ile (c.1977G>A) variant in MYH7
I
Intervention
Correction of the p.Met659Ile (c.1977G>A) variant in MYH7 using CRISPR/Cas9 genome editing
C
Comparator
Unedited patient-specific iPSCs (ICGi019-B) and healthy donor iPSCs (ICGi022-A)
O
Outcome
Generation and characterization of isogenic iPSC lines with the corrected variant (pluripotency, normal karyotype, absence of off-target effects)surrogate

The generation of isogenic iPSC lines with a corrected MYH7 variant provides a valuable tool for studying the pathogenetic mechanisms of hypertrophic cardiomyopathy.

Cite This Study

Shulgina et al. (2025) studied Hypertrophic cardiomyopathy (n=1). CRISPR/Cas9 correction of MYH7 p.Met659Ile variant vs. Uncorrected patient-specific iPSC line was evaluated on Generation of corrected iPSC lines. CRISPR/Cas9 correction of the p.Met659Ile variant in MYH7 in patient-specific iPSCs successfully generated two isogenic iPSC lines that maintained pluripotency and a normal karyotype.

synapsesocial.com/papers/6a1928ac2471b46e09d954eehttps://doi.org/10.18699/vjgb-25-38
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Studying Pathogenetic Contribution of a Variant of Unknown Significance, p.M659I (c.1977G > A) in MYH7, to the Development of Hypertrophic Cardiomyopathy Using CRISPR/Cas9-Engineered Isogenic Induced Pluripotent Stem Cells2024 · 3 citations
  2. 2Generation of Isogenic iPSC Lines for Studying the Effect of the p.N515del (c.1543_1545delAAC) Variant on MYBPC3 Function and Hypertrophic Cardiomyopathy Pathogenesis2024 · 1 citations
  3. 3Generation of an Induced Pluripotent Stem Cell Line ICGi047-A by Reprogramming Peripheral Blood Mononuclear Cells of a Hypertrophic Cardiomyopathy Patient with the Pathogenic Variant c.966G>A in MYBPC3 Gene2025
  4. 4Generation of induced pluripotent stem cells from an individual with early onset and severe hypertrophic cardiomyopathy linked to MYBPC3: c.772G > A mutation2024
  5. 5Abstract Thu036: Generation of induced pluripotent stem cell lines from hypertrophic cardiomyopathy patients carrying MYBPC3 mutations2025