A novel mtDNA point mutation in tRNAVal is associated with hypertrophic cardiomyopathy and MELAS

Francesca Menotti, Agnese Brega, Marta Diegoli, Maurizia Grasso, Maria Grazia Modena, Eloisa Arbustini

Research output: Contribution to journalArticle

Abstract

Background. Pathological mutations of mitochondrial (mt) DNA may cause specific diseases such as cardiomyopathies or hearing loss, or syndromes such as mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome. We describe a novel mtDNA mutation in a patient with severe hypertrophic cardiomyopathy associated with MELAS. The familial phenotype included 1) hypertrophic cardiomyopathy and MELAS, 2) clinically mild cardiac hypertrophy, and 3) deafness. Methods. The proband and her first degree relatives underwent echo and electrocardiograms, and biochemical tests. Magnetic resonance imaging of the brain was performed in the proband. mtDNA was fully analyzed by sequencing. DNA purification, polymerase chain reaction and direct automated sequencing were performed following standard procedures. Heteroplasmy of the novel mutation was quantified by densitometric analysis. Results. A novel G1644A transition affecting the tRNAVal was identified in the proband and maternal relatives. The mutation has been interpreted as pathological because the G at the 1644 position is a highly conserved base, is heteroplasmic with higher levels of mutant DNA in the proband than in the relatives, is located in the unique tRNAVal, is very close to a mutation described as causative of MELAS, and finally has not been found in 100 healthy controls. Conclusions. Although it is rare for patients with MELAS to be referred to cardiological evaluation because of coexisting cardiomyopathy, cardiologists should be aware of this association as well as of the non cardiac signs that may address the diagnosis to mtDNA defect-related disease in families with a variable phenotype.

Original languageEnglish
Pages (from-to)460-465
Number of pages6
JournalItalian Heart Journal
Volume5
Issue number6
Publication statusPublished - Jun 2004

Fingerprint

RNA, Transfer, Val
Lactic Acidosis
Hypertrophic Cardiomyopathy
Brain Diseases
Muscular Diseases
Mitochondrial DNA
Point Mutation
Stroke
Mutation
Cardiomyopathies
MELAS Syndrome
Phenotype
Cardiomegaly
Deafness
DNA-Directed DNA Polymerase
Hearing Loss
Electrocardiography
Mothers
Magnetic Resonance Imaging
Polymerase Chain Reaction

Keywords

  • Hypertrophic cardiomyopathy
  • MELAS
  • MtDNA

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

A novel mtDNA point mutation in tRNAVal is associated with hypertrophic cardiomyopathy and MELAS. / Menotti, Francesca; Brega, Agnese; Diegoli, Marta; Grasso, Maurizia; Modena, Maria Grazia; Arbustini, Eloisa.

In: Italian Heart Journal, Vol. 5, No. 6, 06.2004, p. 460-465.

Research output: Contribution to journalArticle

Menotti, Francesca ; Brega, Agnese ; Diegoli, Marta ; Grasso, Maurizia ; Modena, Maria Grazia ; Arbustini, Eloisa. / A novel mtDNA point mutation in tRNAVal is associated with hypertrophic cardiomyopathy and MELAS. In: Italian Heart Journal. 2004 ; Vol. 5, No. 6. pp. 460-465.
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abstract = "Background. Pathological mutations of mitochondrial (mt) DNA may cause specific diseases such as cardiomyopathies or hearing loss, or syndromes such as mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome. We describe a novel mtDNA mutation in a patient with severe hypertrophic cardiomyopathy associated with MELAS. The familial phenotype included 1) hypertrophic cardiomyopathy and MELAS, 2) clinically mild cardiac hypertrophy, and 3) deafness. Methods. The proband and her first degree relatives underwent echo and electrocardiograms, and biochemical tests. Magnetic resonance imaging of the brain was performed in the proband. mtDNA was fully analyzed by sequencing. DNA purification, polymerase chain reaction and direct automated sequencing were performed following standard procedures. Heteroplasmy of the novel mutation was quantified by densitometric analysis. Results. A novel G1644A transition affecting the tRNAVal was identified in the proband and maternal relatives. The mutation has been interpreted as pathological because the G at the 1644 position is a highly conserved base, is heteroplasmic with higher levels of mutant DNA in the proband than in the relatives, is located in the unique tRNAVal, is very close to a mutation described as causative of MELAS, and finally has not been found in 100 healthy controls. Conclusions. Although it is rare for patients with MELAS to be referred to cardiological evaluation because of coexisting cardiomyopathy, cardiologists should be aware of this association as well as of the non cardiac signs that may address the diagnosis to mtDNA defect-related disease in families with a variable phenotype.",
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N2 - Background. Pathological mutations of mitochondrial (mt) DNA may cause specific diseases such as cardiomyopathies or hearing loss, or syndromes such as mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome. We describe a novel mtDNA mutation in a patient with severe hypertrophic cardiomyopathy associated with MELAS. The familial phenotype included 1) hypertrophic cardiomyopathy and MELAS, 2) clinically mild cardiac hypertrophy, and 3) deafness. Methods. The proband and her first degree relatives underwent echo and electrocardiograms, and biochemical tests. Magnetic resonance imaging of the brain was performed in the proband. mtDNA was fully analyzed by sequencing. DNA purification, polymerase chain reaction and direct automated sequencing were performed following standard procedures. Heteroplasmy of the novel mutation was quantified by densitometric analysis. Results. A novel G1644A transition affecting the tRNAVal was identified in the proband and maternal relatives. The mutation has been interpreted as pathological because the G at the 1644 position is a highly conserved base, is heteroplasmic with higher levels of mutant DNA in the proband than in the relatives, is located in the unique tRNAVal, is very close to a mutation described as causative of MELAS, and finally has not been found in 100 healthy controls. Conclusions. Although it is rare for patients with MELAS to be referred to cardiological evaluation because of coexisting cardiomyopathy, cardiologists should be aware of this association as well as of the non cardiac signs that may address the diagnosis to mtDNA defect-related disease in families with a variable phenotype.

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