Cranioectodermal Dysplasia, Sensenbrenner Syndrome, Is a Ciliopathy Caused by Mutations in the IFT122 Gene

摘要: Cranioectodermal dysplasia (CED) is a disorder characterized by craniofacial, skeletal, and ectodermal abnormalities. Most cases reported to date are sporadic, but few familial support an autosomal-recessive inheritance pattern. Aiming at the elucidation of genetic basis CED, we collected 13 patients with CED symptoms from 12 independent families. In one family consanguineous parents two siblings were affected, permitting linkage analysis homozygosity mapping. This revealed single region significant LOD score (3.57) on chromosome 3q21-3q24. By sequencing candidate genes this interval found homozygous missense mutation in IFT122 (WDR10) gene that cosegregated disease. Examination our patient cohort additional change second family. addition, compound heterozygosity for donor splice-site sporadic patient. All mutations absent 340 control chromosomes. Because plays important role assembly maintenance eukaryotic cilia, investigated fibroblasts significantly reduced frequency length primary cilia as compared controls. Furthermore, we transiently knocked down ift122 zebrafish embryos observed typical phenotype other models ciliopathies. not all harbored IFT122, seems be genetically heterogeneous. Still, identifying CED as ciliary disorder, study suggests causative unresolved most likely affect function too.