title: Autosomal recessive lethal congenital contractural syndrome type 4 (LCCS4) caused by a mutation in MYBPC1.
abstract: Autosomal recessive lethal congenital contractural syndrome (LCCS) is a severe form of neuromuscular arthrogryposis. We previously showed that this phenotype is caused in two unrelated inbred Bedouin tribes by different defects in the phosphatidylinositol pathway. However, the molecular basis of the same phenotype in other tribes remained elusive. Whole exome sequencing identified a novel LCCS founder mutation within a minimal shared homozygosity locus of approximately 1 Mb in two affected individuals of different tribes: a homozygous premature stop producing mutation in MYBPC1, encoding myosin-binding protein C, slow type. A dominant missense mutation in MYBPC1 was previously shown to cause mild distal arthrogryposis. We now show that a recessive mutation abrogating all functional domains in the same gene leads to LCCS.
authors.affiliation: The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev, Ben Gurion University, Beer-Sheva, Israel.
authors.forename: Barak
authors.initials: B
authors.lastname: Markus
authors.forename: Ginat
authors.initials: G
authors.lastname: Narkis
authors.forename: Daniella
authors.initials: D
authors.lastname: Landau
authors.forename: Ruth Z
authors.initials: RZ
authors.lastname: Birk
authors.forename: Idan
authors.initials: I
authors.lastname: Cohen
authors.forename: Ohad S
authors.initials: OS
authors.lastname: Birk
mesh_terms: D001176:Arthrogryposis / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D005804:Genes, Lethal; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010641:Phenotype; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C