Syndactyly is the most common limb defect depicting the bony and/or cutaneous fusion of digits. Syndactyly can be of various types depending on the digits involved in the fusion. To date, eight syndactyly-associated genes have been reported, of which HOXD13 and GJA1 have been explored in a few syndactyly but most of them have unknown underlying genetics. In the present study HOXD13, GJA1 and TP63 genes have been screened by resequencing in 24 unrelated sporadic cases with various syndactyly. The screening revealed two pathogenic HOXD13 variants, NM_000523:c.500 A > G [p.(Y167C)], and NM_000523:c.961 A > C [p.(T321P)] in syndactyly type 1b and type 1c, respectively. This is the first report to identify HOXD13 pathogenic variant in syndactyly type 1b and third report in syndactyly type 1c pathogenesis. Furthermore, this study also reports a TP63 pathogenic variant, NM_003722:c.953 G > A [p.(R318H)] in Ectrodactyly and Cleft lip and palate (ECLP). In conclusion, the current study expands the clinical spectrum of HOXD13 and TP63-related disorders.

并指畸形是最常见的肢体缺陷，表现为手指骨和/或皮肤融合。根据融合中涉及的数字，并指可以是各种类型。迄今为止，已报道了 8 个并指相关基因，其中HOXD13和GJA1已在少数并指相关基因中进行了探索，但其中大多数具有未知的潜在遗传学。在本研究中，HOXD13、GJA1和TP63基因已通过重新测序在 24 例具有各种并指畸形的不相关散发病例中进行筛选。筛查揭示了两种致病性HOXD13变异，NM_000523:c.500 A > G [p.(Y167C)] 和 NM_000523:c.961 A > C [p.(T321P)] 分别在 1b 型和 1c 型并指。这是第一个确定的报告HOXD13在并指1b 型中的致病性变异和在并指 1c 型发病机制中的第三次报告。此外，本研究还报告了外指和唇腭裂 (ECLP) 中的TP63致病性变异，NM_003722 :c.953 G > A [p.(R318H)]。总之，目前的研究扩大了HOXD13和TP63相关疾病的临床范围。