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Background <p>Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic heart disease with a wide range of clinical manifestations, from asymptomatic cases to heart failure and sudden cardiac death.</p> Objectives <p>To identify the disease-causing variants in patients with severe HCM by carrying on clinical examination and genetic analysis through 2 generations in a single family.</p> Patients and methods <p>Family ‘members underwent comprehensive cardiovascular examinations. Whole-exome sequencing was carried on the proband, a girl of five-years old followed by co-segregation and in silico analyses.</p> Results <p>The proband harboured a homozygous variant, NM_022915.5: c.198_205delinsTA; p.(Trp66_His69 delinsCysAsn), in the <i>MRPL44</i> gene, leading to a shorter protein. This variant is novel, being absent in ClinVar and Human Gene Mutation Database (HGMD) and classified as VUS according to American College of Medical Genetics and Genomics (ACMG) criteria. Co-segregation analyses revealed that the proband’s parents and her sister were heterozygous carriers, her other sister was wild-type, and her affected brother was homozygous for the mutation. In silico analysis showed significant structural differences in the mutated mL44 protein, disrupting its interaction with ribosomal complex components and impairing translation and protein synthesis.</p> Conclusions <p>This study reports a novel <i>MRPL44</i> variant associated with HCM in a Tunisian family. This finding expands current knowledge of genetic variations linked to mitochondrial cardiomyopathy and highlights the importance of genetic testing for diagnosis and management of cardiomyopathy.</p>

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A novel likely pathogenic variant in the mitochondrial ribosomal protein L44 (MRPL44) associated with hypertrophic cardiomyopathy in Tunisian patients

  • 期刊论文

  • 发表日期：

    2025年5月22日

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  • Rania Gargouri,
  • Nihel Ammous-Boukhris,
  • Manel Hssairi,
  • Amor Mosbah,
  • Mariem Jabeur,
  • Wiem Feki,
  • Zeineb Mnif,
  • Raja Mokdad-Gargouri,
  • Leila Abid,
  • Lamia Gargouri

摘要

Background

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic heart disease with a wide range of clinical manifestations, from asymptomatic cases to heart failure and sudden cardiac death.

Objectives

To identify the disease-causing variants in patients with severe HCM by carrying on clinical examination and genetic analysis through 2 generations in a single family.

Patients and methods

Family ‘members underwent comprehensive cardiovascular examinations. Whole-exome sequencing was carried on the proband, a girl of five-years old followed by co-segregation and in silico analyses.

Results

The proband harboured a homozygous variant, NM_022915.5: c.198_205delinsTA; p.(Trp66_His69 delinsCysAsn), in the MRPL44 gene, leading to a shorter protein. This variant is novel, being absent in ClinVar and Human Gene Mutation Database (HGMD) and classified as VUS according to American College of Medical Genetics and Genomics (ACMG) criteria. Co-segregation analyses revealed that the proband’s parents and her sister were heterozygous carriers, her other sister was wild-type, and her affected brother was homozygous for the mutation. In silico analysis showed significant structural differences in the mutated mL44 protein, disrupting its interaction with ribosomal complex components and impairing translation and protein synthesis.

Conclusions

This study reports a novel MRPL44 variant associated with HCM in a Tunisian family. This finding expands current knowledge of genetic variations linked to mitochondrial cardiomyopathy and highlights the importance of genetic testing for diagnosis and management of cardiomyopathy.