Identification of a novel MYBPC3 gene variant in a patient with hypertrophic cardiomyopathy

Maria Brion, Catarina Allegue, Rocio Gil, Alejandro Blanco-Verea, Angel Carracedo, Erika Pagannone, Anna Evangelista, Sara Di Castro, Simona Marchitti, Rosita Stanzione, Massimo Volpe, Speranza Rubattu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by cardiac hypertrophy caused by mutations in sarcomere protein genes. MYBPC3 mutations are reported as a frequent cause of HCM. We aimed to identify the gene mutation underlying HCM in an Italian patient and his family composed of 13 relatives. Mutation screening of 658 known mutations was performed using a rapid and efficient mutation detection system based on semiautomated MALDI-TOF mass spectrometry using the Sequenom MassArray System and iPLEX Gold genotyping chemistry. Subsequently, direct sequencing of the coding exons and flanking intronic regions was performed for the most suitable HCM genes (MYBPC3, MYH7, TNNT2, TNNI3, and TPM1) in the index patient. We found a novel MYBPC3 gene mutation: G13999T (Gln689His). No other sarcomere gene mutation was found in this family. This genetic variant, which changes the last amino acid of MYBPC3 exon 21, affects a highly conserved residue. Furthermore, the Gln689His does not appear in public databases and has never been described as a polymorphism. The potential pathogenic role of this novel mutation was underlined by its absence in a sample of healthy subjects (n = 122) from the general Italian population. In summary, a novel MYBPC3 gene mutation has been identified in a patient affected by HCM, whereas it was absent in 244 reference alleles.

Original languageEnglish
Pages (from-to)285-289
Number of pages5
JournalAnnals of Clinical and Laboratory Science
Volume40
Issue number3
Publication statusPublished - Jun 2010

Fingerprint

Hypertrophic Cardiomyopathy
Genes
Mutation
Exons
Sarcomeres
Polymorphism
Gold
Mass spectrometry
Screening
Amino Acids
Inborn Genetic Diseases
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Cardiomegaly
Mass Spectrometry
Healthy Volunteers
Proteins
Alleles
Databases

Keywords

  • Cardiac hypertrophy
  • Gene mutation
  • Myosin binding protein C

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Immunology
  • Microbiology
  • Hematology
  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Medical Laboratory Technology

Cite this

Brion, M., Allegue, C., Gil, R., Blanco-Verea, A., Carracedo, A., Pagannone, E., ... Rubattu, S. (2010). Identification of a novel MYBPC3 gene variant in a patient with hypertrophic cardiomyopathy. Annals of Clinical and Laboratory Science, 40(3), 285-289.

Identification of a novel MYBPC3 gene variant in a patient with hypertrophic cardiomyopathy. / Brion, Maria; Allegue, Catarina; Gil, Rocio; Blanco-Verea, Alejandro; Carracedo, Angel; Pagannone, Erika; Evangelista, Anna; Di Castro, Sara; Marchitti, Simona; Stanzione, Rosita; Volpe, Massimo; Rubattu, Speranza.

In: Annals of Clinical and Laboratory Science, Vol. 40, No. 3, 06.2010, p. 285-289.

Research output: Contribution to journalArticle

Brion, M, Allegue, C, Gil, R, Blanco-Verea, A, Carracedo, A, Pagannone, E, Evangelista, A, Di Castro, S, Marchitti, S, Stanzione, R, Volpe, M & Rubattu, S 2010, 'Identification of a novel MYBPC3 gene variant in a patient with hypertrophic cardiomyopathy', Annals of Clinical and Laboratory Science, vol. 40, no. 3, pp. 285-289.
Brion M, Allegue C, Gil R, Blanco-Verea A, Carracedo A, Pagannone E et al. Identification of a novel MYBPC3 gene variant in a patient with hypertrophic cardiomyopathy. Annals of Clinical and Laboratory Science. 2010 Jun;40(3):285-289.
Brion, Maria ; Allegue, Catarina ; Gil, Rocio ; Blanco-Verea, Alejandro ; Carracedo, Angel ; Pagannone, Erika ; Evangelista, Anna ; Di Castro, Sara ; Marchitti, Simona ; Stanzione, Rosita ; Volpe, Massimo ; Rubattu, Speranza. / Identification of a novel MYBPC3 gene variant in a patient with hypertrophic cardiomyopathy. In: Annals of Clinical and Laboratory Science. 2010 ; Vol. 40, No. 3. pp. 285-289.
@article{7a902ae6d98b432c9a09e62009cbe300,
title = "Identification of a novel MYBPC3 gene variant in a patient with hypertrophic cardiomyopathy",
abstract = "Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by cardiac hypertrophy caused by mutations in sarcomere protein genes. MYBPC3 mutations are reported as a frequent cause of HCM. We aimed to identify the gene mutation underlying HCM in an Italian patient and his family composed of 13 relatives. Mutation screening of 658 known mutations was performed using a rapid and efficient mutation detection system based on semiautomated MALDI-TOF mass spectrometry using the Sequenom MassArray System and iPLEX Gold genotyping chemistry. Subsequently, direct sequencing of the coding exons and flanking intronic regions was performed for the most suitable HCM genes (MYBPC3, MYH7, TNNT2, TNNI3, and TPM1) in the index patient. We found a novel MYBPC3 gene mutation: G13999T (Gln689His). No other sarcomere gene mutation was found in this family. This genetic variant, which changes the last amino acid of MYBPC3 exon 21, affects a highly conserved residue. Furthermore, the Gln689His does not appear in public databases and has never been described as a polymorphism. The potential pathogenic role of this novel mutation was underlined by its absence in a sample of healthy subjects (n = 122) from the general Italian population. In summary, a novel MYBPC3 gene mutation has been identified in a patient affected by HCM, whereas it was absent in 244 reference alleles.",
keywords = "Cardiac hypertrophy, Gene mutation, Myosin binding protein C",
author = "Maria Brion and Catarina Allegue and Rocio Gil and Alejandro Blanco-Verea and Angel Carracedo and Erika Pagannone and Anna Evangelista and {Di Castro}, Sara and Simona Marchitti and Rosita Stanzione and Massimo Volpe and Speranza Rubattu",
year = "2010",
month = "6",
language = "English",
volume = "40",
pages = "285--289",
journal = "Annals of Clinical and Laboratory Science",
issn = "0091-7370",
publisher = "Association of Clinical Scientists",
number = "3",

}

TY - JOUR

T1 - Identification of a novel MYBPC3 gene variant in a patient with hypertrophic cardiomyopathy

AU - Brion, Maria

AU - Allegue, Catarina

AU - Gil, Rocio

AU - Blanco-Verea, Alejandro

AU - Carracedo, Angel

AU - Pagannone, Erika

AU - Evangelista, Anna

AU - Di Castro, Sara

AU - Marchitti, Simona

AU - Stanzione, Rosita

AU - Volpe, Massimo

AU - Rubattu, Speranza

PY - 2010/6

Y1 - 2010/6

N2 - Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by cardiac hypertrophy caused by mutations in sarcomere protein genes. MYBPC3 mutations are reported as a frequent cause of HCM. We aimed to identify the gene mutation underlying HCM in an Italian patient and his family composed of 13 relatives. Mutation screening of 658 known mutations was performed using a rapid and efficient mutation detection system based on semiautomated MALDI-TOF mass spectrometry using the Sequenom MassArray System and iPLEX Gold genotyping chemistry. Subsequently, direct sequencing of the coding exons and flanking intronic regions was performed for the most suitable HCM genes (MYBPC3, MYH7, TNNT2, TNNI3, and TPM1) in the index patient. We found a novel MYBPC3 gene mutation: G13999T (Gln689His). No other sarcomere gene mutation was found in this family. This genetic variant, which changes the last amino acid of MYBPC3 exon 21, affects a highly conserved residue. Furthermore, the Gln689His does not appear in public databases and has never been described as a polymorphism. The potential pathogenic role of this novel mutation was underlined by its absence in a sample of healthy subjects (n = 122) from the general Italian population. In summary, a novel MYBPC3 gene mutation has been identified in a patient affected by HCM, whereas it was absent in 244 reference alleles.

AB - Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by cardiac hypertrophy caused by mutations in sarcomere protein genes. MYBPC3 mutations are reported as a frequent cause of HCM. We aimed to identify the gene mutation underlying HCM in an Italian patient and his family composed of 13 relatives. Mutation screening of 658 known mutations was performed using a rapid and efficient mutation detection system based on semiautomated MALDI-TOF mass spectrometry using the Sequenom MassArray System and iPLEX Gold genotyping chemistry. Subsequently, direct sequencing of the coding exons and flanking intronic regions was performed for the most suitable HCM genes (MYBPC3, MYH7, TNNT2, TNNI3, and TPM1) in the index patient. We found a novel MYBPC3 gene mutation: G13999T (Gln689His). No other sarcomere gene mutation was found in this family. This genetic variant, which changes the last amino acid of MYBPC3 exon 21, affects a highly conserved residue. Furthermore, the Gln689His does not appear in public databases and has never been described as a polymorphism. The potential pathogenic role of this novel mutation was underlined by its absence in a sample of healthy subjects (n = 122) from the general Italian population. In summary, a novel MYBPC3 gene mutation has been identified in a patient affected by HCM, whereas it was absent in 244 reference alleles.

KW - Cardiac hypertrophy

KW - Gene mutation

KW - Myosin binding protein C

UR - http://www.scopus.com/inward/record.url?scp=77955808124&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955808124&partnerID=8YFLogxK

M3 - Article

C2 - 20689143

AN - SCOPUS:77955808124

VL - 40

SP - 285

EP - 289

JO - Annals of Clinical and Laboratory Science

JF - Annals of Clinical and Laboratory Science

SN - 0091-7370

IS - 3

ER -