Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome

Fukiko Ichida, Shinichi Tsubata, Karla R. Bowles, Noriyuki Haneda, Keiichiro Uese, Toshio Miyawaki, W. Jeffrey Dreyer, John Messina, Hua Li, Neil E. Bowles, Jeffrey Towbin

Research output: Contribution to journalArticle

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Abstract

Background - Mutations in the gene G4.5 result in a wide spectrum of severe infantile cardiomyopathic phenotypes, including isolated left ventricular noncompaction (LVNC), as well as Barth syndrome (BTHS) with dilated cardiomyopathy (DCM). The purpose of this study was to investigate patients with LVNC or BTHS for mutations in G4.5 or other novel genes. Methods and Results - DNA was isolated from 2 families and 3 individuals with isolated LVNC or LVNC with congenital heart disease (CHD), as well as 4 families with BTHS associated with LVNC or DCM, and screened for mutations by single-strand DNA conformation polymorphism analysis and DNA sequencing. In 1 family with LVNC and CHD, a C→T mutation was identified at nucleotide 362 of α-dystrobrevin, changing a proline to leucine (P121L). Mutations in G4.5 were identified in 2 families with isolated LVNC: a missense mutation in exon 4 (C118R) in 1 and a splice donor mutation (IVS10+2T→A) in intron 10 in the other. In a family with cardiomyopathies ranging from BTHS or fatal infantile cardiomyopathy to asymptomatic DCM, a splice acceptor mutation in exon 2 of G4.5 (398-2 A→G) was identified, and a 1-bp deletion in exon 2 of G4.5, resulting in a stop codon after amino acid 41, was identified in a sporadic case of BTHS. Conclusions - These data demonstrate genetic heterogeneity in LVNC, with mutation of a novel gene, α-dystrobrevin, identified in LVNC associated with CHD. In addition, these results confirm that mutations in G4.5 result in a wide phenotypic spectrum of cardiomyopathies.

Original languageEnglish (US)
Pages (from-to)1256-1263
Number of pages8
JournalCirculation
Volume103
Issue number9
DOIs
StatePublished - Mar 6 2001
Externally publishedYes

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Barth Syndrome
Mutation
Genes
Cardiomyopathies
Exons
Heart Diseases
Dilated Cardiomyopathy
Nucleic Acid Conformation
Genetic Heterogeneity
Terminator Codon
Missense Mutation
DNA Sequence Analysis
Proline
Leucine
Introns
Nucleotides

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Ichida, F., Tsubata, S., Bowles, K. R., Haneda, N., Uese, K., Miyawaki, T., ... Towbin, J. (2001). Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation, 103(9), 1256-1263. https://doi.org/10.1161/01.CIR.103.9.1256

Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. / Ichida, Fukiko; Tsubata, Shinichi; Bowles, Karla R.; Haneda, Noriyuki; Uese, Keiichiro; Miyawaki, Toshio; Dreyer, W. Jeffrey; Messina, John; Li, Hua; Bowles, Neil E.; Towbin, Jeffrey.

In: Circulation, Vol. 103, No. 9, 06.03.2001, p. 1256-1263.

Research output: Contribution to journalArticle

Ichida, F, Tsubata, S, Bowles, KR, Haneda, N, Uese, K, Miyawaki, T, Dreyer, WJ, Messina, J, Li, H, Bowles, NE & Towbin, J 2001, 'Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome', Circulation, vol. 103, no. 9, pp. 1256-1263. https://doi.org/10.1161/01.CIR.103.9.1256
Ichida F, Tsubata S, Bowles KR, Haneda N, Uese K, Miyawaki T et al. Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation. 2001 Mar 6;103(9):1256-1263. https://doi.org/10.1161/01.CIR.103.9.1256
Ichida, Fukiko ; Tsubata, Shinichi ; Bowles, Karla R. ; Haneda, Noriyuki ; Uese, Keiichiro ; Miyawaki, Toshio ; Dreyer, W. Jeffrey ; Messina, John ; Li, Hua ; Bowles, Neil E. ; Towbin, Jeffrey. / Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. In: Circulation. 2001 ; Vol. 103, No. 9. pp. 1256-1263.
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abstract = "Background - Mutations in the gene G4.5 result in a wide spectrum of severe infantile cardiomyopathic phenotypes, including isolated left ventricular noncompaction (LVNC), as well as Barth syndrome (BTHS) with dilated cardiomyopathy (DCM). The purpose of this study was to investigate patients with LVNC or BTHS for mutations in G4.5 or other novel genes. Methods and Results - DNA was isolated from 2 families and 3 individuals with isolated LVNC or LVNC with congenital heart disease (CHD), as well as 4 families with BTHS associated with LVNC or DCM, and screened for mutations by single-strand DNA conformation polymorphism analysis and DNA sequencing. In 1 family with LVNC and CHD, a C→T mutation was identified at nucleotide 362 of α-dystrobrevin, changing a proline to leucine (P121L). Mutations in G4.5 were identified in 2 families with isolated LVNC: a missense mutation in exon 4 (C118R) in 1 and a splice donor mutation (IVS10+2T→A) in intron 10 in the other. In a family with cardiomyopathies ranging from BTHS or fatal infantile cardiomyopathy to asymptomatic DCM, a splice acceptor mutation in exon 2 of G4.5 (398-2 A→G) was identified, and a 1-bp deletion in exon 2 of G4.5, resulting in a stop codon after amino acid 41, was identified in a sporadic case of BTHS. Conclusions - These data demonstrate genetic heterogeneity in LVNC, with mutation of a novel gene, α-dystrobrevin, identified in LVNC associated with CHD. In addition, these results confirm that mutations in G4.5 result in a wide phenotypic spectrum of cardiomyopathies.",
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AU - Ichida, Fukiko

AU - Tsubata, Shinichi

AU - Bowles, Karla R.

AU - Haneda, Noriyuki

AU - Uese, Keiichiro

AU - Miyawaki, Toshio

AU - Dreyer, W. Jeffrey

AU - Messina, John

AU - Li, Hua

AU - Bowles, Neil E.

AU - Towbin, Jeffrey

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N2 - Background - Mutations in the gene G4.5 result in a wide spectrum of severe infantile cardiomyopathic phenotypes, including isolated left ventricular noncompaction (LVNC), as well as Barth syndrome (BTHS) with dilated cardiomyopathy (DCM). The purpose of this study was to investigate patients with LVNC or BTHS for mutations in G4.5 or other novel genes. Methods and Results - DNA was isolated from 2 families and 3 individuals with isolated LVNC or LVNC with congenital heart disease (CHD), as well as 4 families with BTHS associated with LVNC or DCM, and screened for mutations by single-strand DNA conformation polymorphism analysis and DNA sequencing. In 1 family with LVNC and CHD, a C→T mutation was identified at nucleotide 362 of α-dystrobrevin, changing a proline to leucine (P121L). Mutations in G4.5 were identified in 2 families with isolated LVNC: a missense mutation in exon 4 (C118R) in 1 and a splice donor mutation (IVS10+2T→A) in intron 10 in the other. In a family with cardiomyopathies ranging from BTHS or fatal infantile cardiomyopathy to asymptomatic DCM, a splice acceptor mutation in exon 2 of G4.5 (398-2 A→G) was identified, and a 1-bp deletion in exon 2 of G4.5, resulting in a stop codon after amino acid 41, was identified in a sporadic case of BTHS. Conclusions - These data demonstrate genetic heterogeneity in LVNC, with mutation of a novel gene, α-dystrobrevin, identified in LVNC associated with CHD. In addition, these results confirm that mutations in G4.5 result in a wide phenotypic spectrum of cardiomyopathies.

AB - Background - Mutations in the gene G4.5 result in a wide spectrum of severe infantile cardiomyopathic phenotypes, including isolated left ventricular noncompaction (LVNC), as well as Barth syndrome (BTHS) with dilated cardiomyopathy (DCM). The purpose of this study was to investigate patients with LVNC or BTHS for mutations in G4.5 or other novel genes. Methods and Results - DNA was isolated from 2 families and 3 individuals with isolated LVNC or LVNC with congenital heart disease (CHD), as well as 4 families with BTHS associated with LVNC or DCM, and screened for mutations by single-strand DNA conformation polymorphism analysis and DNA sequencing. In 1 family with LVNC and CHD, a C→T mutation was identified at nucleotide 362 of α-dystrobrevin, changing a proline to leucine (P121L). Mutations in G4.5 were identified in 2 families with isolated LVNC: a missense mutation in exon 4 (C118R) in 1 and a splice donor mutation (IVS10+2T→A) in intron 10 in the other. In a family with cardiomyopathies ranging from BTHS or fatal infantile cardiomyopathy to asymptomatic DCM, a splice acceptor mutation in exon 2 of G4.5 (398-2 A→G) was identified, and a 1-bp deletion in exon 2 of G4.5, resulting in a stop codon after amino acid 41, was identified in a sporadic case of BTHS. Conclusions - These data demonstrate genetic heterogeneity in LVNC, with mutation of a novel gene, α-dystrobrevin, identified in LVNC associated with CHD. In addition, these results confirm that mutations in G4.5 result in a wide phenotypic spectrum of cardiomyopathies.

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