A homozygous premature stop mutation in MYBPC1 was identified via whole exome sequencing as the cause of autosomal recessive lethal congenital contractural syndrome in 2 affected individuals.
Observational (n=2)
A recessive mutation abrogating all functional domains in MYBPC1 leads to lethal congenital contractural syndrome (LCCS).
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.
Markus et al. (Fri,) conducted a observational in Autosomal recessive lethal congenital contractural syndrome (LCCS) (n=2). Whole exome sequencing was evaluated on Identification of the molecular basis of LCCS. A homozygous premature stop mutation in MYBPC1 was identified via whole exome sequencing as the cause of autosomal recessive lethal congenital contractural syndrome in 2 affected individuals.