The truncated GLI3 p.Gln247∗ (c.739C > T) protein was detectable in the patients, and it can constitutively block the SHH signaling pathway, abrogate the function of GLI3, lead to the loss of binding ability with SUFU, restrain GLI3 from entry into the nucleus as a regulator, and influence the expression of key functional proteins of the SHH signaling pathway in a family with polydactyly and syndactyly. Here, SHH is linked to polydactyly.