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Updated: Aug 15, 2025
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Severe hypertrophic cardiomyopathy in a patient with a homozygous MYH7 gene variant
Walter Serra1, Giulia Vitetta2, Vera Uliana2
1Cardiology Division, University Hospital of Parma, Italy.
Insights
A homozygous MYH7 gene variant caused early hypertrophic cardiomyopathy (HCM) in a young patient. Heterozygous variants in relatives showed milder cardiac phenotypes, suggesting a gene dosage effect in HCM development.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Genetic Diseases
Background:
- Hypertrophic cardiomyopathy (HCM) is an autosomal dominant cardiac disorder characterized by unexplained left ventricular hypertrophy.
- The interventricular septum is often asymmetrically thickened, particularly in the basal region.
- Genetic factors play a crucial role in the pathogenesis of HCM.
Observation:
- A 17-year-old patient presented with concentric left ventricular parietal hypertrophy and a 23 mm interventricular septum thickness.
- Genetic counseling revealed a family history of hypertrophic cardiac disease and parental consanguinity.
- A homozygous c.3424G>A (p.Glu1142Lys) variant in the MYH7 gene was identified in the patient.
Findings:
- The homozygous MYH7 variant was associated with early-onset, severe hypertrophic cardiomyopathy.
- Heterozygous carriers of the MYH7 variant in the family exhibited milder cardiac phenotypes.
- The severity of HCM correlated with the zygosity state of the MYH7 variant, indicating a gene dosage effect.
Implications:
- This case highlights the significant impact of homozygous pathogenic variants in sarcomeric genes on cardiac morphology and function.
- Understanding gene dosage effects is crucial for accurate diagnosis and prognosis of inherited cardiomyopathies.
- Genetic testing and counseling are vital for families with a history of hypertrophic cardiomyopathy.
Background:
Hypertrophic cardiomyopathy is an autosomal dominant disease. The main feature of this disorder is its occurrence in patients who present a left ventricular hypertrophy, unexplained by the loading conditions, usually asymmetric with greatest involvement most commonly of the interventricular septum.Case presentation During a sports medicine control, a ultrasound scan in a 17 years old patient has shown a concentric left ventricular parietal hypertrophy associated with a 23 mm mid- basal interventricular septum thickness. After genetic counselling, a positive family history for hypertrophic cardiac disease and parents' consanguineity was found. The genetic basis of the hypertrophic cardiomyopathy was investigated through a dedicated gene panel. The genetic test has revealed the presence of the variant c.3424G>A (p.Glu1142Lys) in the MYH7 gene in a homozygous state. Genotyping of the parents and of the two brothers revealed the presence of the MYH7 variant in heterozygosity in both parents and in the younger brother. In all of them, variable signs of hypertrophic cardiomyopathy were found.
Conclusions:
Our findings report the presence of a homozygous variant in a sarcomeric gene (MYH7) which gave rise to early HCM, whereas the variant in a heterozygous state was associated to much milder cardiac phenotypes in the affected relatives. The onset and the progression of the hypertrophic cardiomyopathy in the reported family is to be referred to the presence of the variant in hetero- or homo-zygosity in a gene dosage manner.
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