A rare Gollop-Wolfgang Syndrome linked to a mutation in Wnt11

Abstract Gollop-Wolfgang syndrome (GWS) is a rare congenital limb anomaly of unknown genetic background, characterized by a tibial aplasia, ipsilateral bifurcation of the thigh bone, and an ectrodactyly. A phenotypically similar condition is called Split-hand/foot malformation associated with aplasia of long bones (SHFLD). Several hotspots on chromosome 17 have been linked to SHFLD phenotype. Some of them, like duplications described within BHLHA9, are associated both with ectrodactyly and tibial aplasia. Nonetheless, no single mutation linking all known GWS patients has been identified yet. We studied a three-generation family with four GWS-affected family members. Analysis of whole genome sequencing with a custom pipeline indicated that WNT11 c.1015G>A mutation could cause the observed phenotype. Further, in silico modeling and luciferase assay supported WNT11 c.1015G>A mutation effect on Wnt11 functionality.