Polydactyly Patient Carried a Mutation of PTCH1 Which Has Been Identified in Nevoid Basal Cell Nevus Syndrome

Polydactyly frequently exhibits autosomal dominant inheritance, which is characterized by supernumerary fingers or toes. The growth of the limb was controlled by three signaling pathways in three-dimensional axis. Sonic Hedgehog signaling, which controls the anterior to posterior (radial to ulnar) orientation has been suspected to be a main cause for polydactyly. To determine the pathogenesis of the patients with polydactyly, we recruited a polydactyly family with two patients. Taking advantage of next-generation sequencing technology, we applied whole-exome sequencing and Sanger sequencing to the proband and her daughter. The analysis of the whole-exome sequencing showed a heterozygous missense mutation c.3617G>A (p.R1206H) in the PTCH1 gene. The results of Sanger sequencing also verified this mutation. Our research discovered a candidate gene of polydactyly-PTCH1. We are the first to point out the relationship between polydactyly and PTCH1 mutation in human. As the PTCH1 gene mutations have been identified in nevoid basal cell nevus syndrome (NBCCS), and polydactyly is one phenotype of NBCCS, it may provide a new clue to the study of the genotype-phenotype correlations between the PTCH1 gene mutations and NBCCS.