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.

中文翻译：

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多发性畸形患者携带了已在空基细胞痣综合征中鉴定出的PTCH1突变。

多指经常表现出常染色体显性遗传，其特征是手指或脚趾过多​​。肢体的生长由三维轴上的三个信号通路控制。控制前到后（signaling骨至尺骨）方向的声波刺猬信号被怀疑是多指畸形的主要原因。为了确定多指患者的发病机理，我们招募了一个有两个患者的多指家庭。利用下一代测序技术，我们对先证者和她的女儿进行了全外显子测序和Sanger测序。全外显子组测序分析显示PTCH1中存在杂合错义突变c.3617G> A（p.R1206H）基因。Sanger测序的结果也证实了该突变。我们的研究发现了多指候选基因PTCH1。我们是第一个指出人类多态性与PTCH1突变之间的关系的人。由于已经在无基底细胞痣综合征（NBCCS）中鉴定出PTCH1基因突变，并且多态性是NBCCS的一种表型，它可能为研究PTCH1基因突变与NBCCS之间的基因型-表型相关性提供新的线索。