Gollop-Wolfgang complex (GWC) is a rare congenital limb anomaly characterized by tibial aplasia with femur bifurcation, ipsilateral bifurcation of the thigh bone, and split hand and monodactyly of the feet, resulting in severe and complex limb deformities. The genetic basis of GWC, however, has remained elusive. We studied a three-generation family with four GWC-affected family members. An analysis of whole-genome sequencing results using a custom pipeline identified the WNT11 c.1015G>A missense variant associated with the phenotype. In silico modelling and an in vitro reporter assay further supported the link between the variant and GWC. This finding further contributes to mapping the genetic heterogeneity underlying split hand/foot malformations in general and in GWC specifically.
Keywords: Gollop–Wolfgang complex; WNT11; split-hand/foot malformation; whole genome sequencing.