We report novel causative mutations in the IFT80 gene identified in four fetuses from two unrelated families with Beemer-Langer syndrome (BLS) or BLS-like phenotypes. We discuss the implication of the IFT80 gene in ciliopathies, and its diagnostic value for BLS among other SRPS.

Since most short-rib polydactyly phenotypes are due to genes involved with biogenesis and maintenance of the primary cilium, this group of skeletal dysplasias was recently designated as ciliopathies with major skeletal involvement. Beemer-Langer syndrome or short-rib polydactyly type IV, was first described in 1983, and has, thus far, remained without a defined molecular basis. The most recent classification of the skeletal dysplasias referred to this phenotype as an as-yet unproven ciliopathy. IFT122 is a gene that encodes a protein responsible for the retrograde transport along the cilium; it has been associated with this group of skeletal dysplasias. To date, mutations in this gene were only found in Sensenbrenner syndrome. Using a panel of skeletal dysplasias genes, including 11 related to SRP, we identified biallelic mutations in IFT122 ([c.3184G>C];[c.3228dupG;c.3231_3233delCAT]) in a fetus with a typical phenotype of SRP-IV, finally confirmed that this phenotype is a ciliopathy and adding to the list of ciliopathies with major skeletal involvement.