Mutations in DYNC2LI1 disrupt cilia function and cause short rib polydactyly syndrome

摘要: The short rib polydactyly syndromes (SRPSs) are a heterogeneous group of autosomal recessive, perinatal lethal skeletal disorders characterized primarily by short, horizontal ribs, limbs and polydactyly. Mutations in several genes affecting intraflagellar transport (IFT) cause SRPS but they do not account for all cases. Here we identify an additional gene further unravel the functional basis IFT. We perform whole-exome sequencing mutations new disease-producing gene, cytoplasmic dynein-2 light intermediate chain 1, DYNC2LI1, segregating with disease three families. Using primary fibroblasts, show that DYNC2LI1 is essential complex stability result variable length, including hyperelongated, cilia, Hedgehog pathway impairment ciliary IFT accumulations. findings this study expand our understanding locus heterogeneity demonstrate importance stability, cilium function, regulation skeletogenesis.