Syndactyly is one of the most common hereditary limb malformations, and is characterized by the fusion of specific fingers and/or toes. Syndactyly type I‑c is associated with bilateral cutaneous or bony webbing of the third and fourth fingers and occasionally of the third to fifth fingers, with normal feet. The aim of the present study was to identify the genetic basis of syndactyly type I‑c in four generations of a Chinese Han family by exome sequencing. Exome sequencing was conducted in the proband of the family, followed by direct sequencing of other family members of the same ancestry, as well as 100 ethnically‑matched, unrelated normal controls. A missense mutation, c.917G>A (p.R306Q), was identified in the homeobox D13 gene (HOXD13). Sanger sequencing verified the presence of this mutation in all of the affected family members. By contrast, this mutation was absent in the unaffected family members and the 100 ethnically‑matched normal controls. The results suggest that the c.917G>A (p.R306Q) mutation in the HOXD13 gene, may be responsible for syndactyly type I‑c in this family. Exome sequencing may therefore be a powerful tool for identifying mutations associated with syndactyly, which is a disorder with high genetic and clinical heterogeneity. The results provide novel insights into the etiology and diagnosis of syndactyly, and may influence genetic counseling and the clinical management of the disease.