RGD Reference Report - Noncompaction of the ventricular myocardium is associated with a de novo mutation in the beta-myosin heavy chain gene. - Rat Genome Database

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Noncompaction of the ventricular myocardium is associated with a de novo mutation in the beta-myosin heavy chain gene.

Authors: Budde, BS  Binner, P  Waldmuller, S  Hohne, W  Blankenfeldt, W  Hassfeld, S  Bromsen, J  Dermintzoglou, A  Wieczorek, M  May, E  Kirst, E  Selignow, C  Rackebrandt, K  Muller, M  Goody, RS  Vosberg, HP  Nurnberg, P  Scheffold, T 
Citation: Budde BS, etal., PLoS One. 2007 Dec 26;2(12):e1362.
RGD ID: 11098258
Pubmed: PMID:18159245   (View Abstract at PubMed)
PMCID: PMC2137931   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0001362   (Journal Full-text)

Noncompaction of the ventricular myocardium (NVM) is the morphological hallmark of a rare familial or sporadic unclassified heart disease of heterogeneous origin. NVM results presumably from a congenital developmental error and has been traced back to single point mutations in various genes. The objective of this study was to determine the underlying genetic defect in a large German family suffering from NVM. Twenty four family members were clinically assessed using advanced imaging techniques. For molecular characterization, a genome-wide linkage analysis was undertaken and the disease locus was mapped to chromosome 14ptel-14q12. Subsequently, two genes of the disease interval, MYH6 and MYH7 (encoding the alpha- and beta-myosin heavy chain, respectively) were sequenced, leading to the identification of a previously unknown de novo missense mutation, c.842G>C, in the gene MYH7. The mutation affects a highly conserved amino acid in the myosin subfragment-1 (R281T). In silico simulations suggest that the mutation R281T prevents the formation of a salt bridge between residues R281 and D325, thereby destabilizing the myosin head. The mutation was exclusively present in morphologically affected family members. A few members of the family displayed NVM in combination with other heart defects, such as dislocation of the tricuspid valve (Ebstein's anomaly, EA) and atrial septal defect (ASD). A high degree of clinical variability was observed, ranging from the absence of symptoms in childhood to cardiac death in the third decade of life. The data presented in this report provide first evidence that a mutation in a sarcomeric protein can cause noncompaction of the ventricular myocardium.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MYH7Humancongenital heart disease  IAGP DNA:missense mutation:exon:p.R281T (c.842G>C) (human)RGD 
Myh7Ratcongenital heart disease  ISOMYH7 (Homo sapiens)DNA:missense mutation:exon:p.R281T (c.842G>C) (human)RGD 
Myh7Mousecongenital heart disease  ISOMYH7 (Homo sapiens)DNA:missense mutation:exon:p.R281T (c.842G>C) (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MYH7HumanAbnormal EKG  IAGP DNA:missense mutation:exon:p.R281T (c.842G>C)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Myh7  (myosin heavy chain 7)

Genes (Mus musculus)
Myh7  (myosin, heavy polypeptide 7, cardiac muscle, beta)

Genes (Homo sapiens)
MYH7  (myosin heavy chain 7)


Additional Information