2012/05/18 by Barak Markus, Ginat Narkis, Daniella Landau +4
Biochemistry, Genetics and Molecular Biology · Medicine · #Cardiomyopathy and Myosin Studies #Muscle Physiology and Disorders #Neurogenetic and Muscular Disorders Research
paper · doi:10.1002/humu.22122
openalex publication_date 2012/05/18 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
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.