title: Organization and sequence of human cardiac myosin binding protein C gene (MYBPC3) and identification of mutations predicted to produce truncated proteins in familial hypertrophic cardiomyopathy.
abstract: Cardiac myosin binding protein C (MyBP-C) is a sarcomeric protein belonging to the intracellular immunoglobulin superfamily. Its function is uncertain, but for a decade evidence has existed for both structural and regulatory roles. The gene encoding cardiac MyBP-C (MYBPC3) in humans is located on chromosome 11p11.2, and mutations have been identified in this gene in unrelated families with familial hypertrophic cardiomyopathy (FHC). Detailed characterization of the MYBPC3 gene is essential for studies on gene regulation, analysis of the role of MyBP-C in cardiac contraction through the use of recombinant DNA technology, and mutational analyses of FHC. The organization of human MYBPC3 and screening for mutations in a panel of French families with FHC were established using polymerase chain reaction, single-strand conformation polymorphism, and sequencing. The MYBPC3 gene comprises > 21,000 base pairs and contains 35 exons. Two exons are unusually small in size, 3 bp each. We found six new mutations associated with FHC in seven unrelated French families. Four of these mutations are predicted to produce truncated cardiac MyBP-C polypeptides. The two others should each produce two aberrant proteins, one truncated and one mutated. The present study provides the first organization and sequence for an MyBP-C gene. The mutations reported here and previously in MYBPC3 result in aberrant transcripts that are predicted to encode significantly truncated cardiac MyBP-C polypeptides. This spectrum of mutations differs from the ones previously observed in other disease genes causing FHC. Our data strengthen the functional importance of MyBP-C in the regulation of cardiac work and provide the basis for further studies.
authors.affiliation: Unité de Recherches 153 de l'INSERM, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. lcarrier@myologie.infobiogen.fr
authors.forename: L
authors.initials: L
authors.lastname: Carrier
authors.forename: G
authors.initials: G
authors.lastname: Bonne
authors.forename: E
authors.initials: E
authors.lastname: Bährend
authors.forename: B
authors.initials: B
authors.lastname: Yu
authors.forename: P
authors.initials: P
authors.lastname: Richard
authors.forename: F
authors.initials: F
authors.lastname: Niel
authors.forename: B
authors.initials: B
authors.lastname: Hainque
authors.forename: C
authors.initials: C
authors.lastname: Cruaud
authors.forename: F
authors.initials: F
authors.lastname: Gary
authors.forename: S
authors.initials: S
authors.lastname: Labeit
authors.forename: J B
authors.initials: JB
authors.lastname: Bouhour
authors.forename: O
authors.initials: O
authors.lastname: Dubourg
authors.forename: M
authors.initials: M
authors.lastname: Desnos
authors.forename: A A
authors.initials: AA
authors.lastname: Hagège
authors.forename: R J
authors.initials: RJ
authors.lastname: Trent
authors.forename: M
authors.initials: M
authors.lastname: Komajda
authors.forename: M
authors.initials: M
authors.lastname: Fiszman
authors.forename: K
authors.initials: K
authors.lastname: Schwartz
mesh_terms: D001483:Base Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D017931:DNA Primers; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D017421:Sequence Analysis; D017384:Sequence Deletion; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D000099163:Myosin Binding Protein C