A novel non-synonymous mutation in the homeodomain of HOXD13 causes synpolydactyly in a Chinese family.

Purpose: The 5' HoxD genes and their paralogs in the HoxD cluster are crucial for normal vertebrate limb development. Mutations in HOXD13 and HOXD13 have been found to cause human limb malformation. Here we describe a two-generation Chinese family with a variant form of mild synpolydactyly.
Methods: Sequence analysis of HOXD13 gene in a two-generation Chinese family with six individuals.
Results: Gene scan and linkage analysis suggested that HOXD13 might be responsible for the disease of this family. An LOD around 1.8 was observed at three markers (P=2E(-3)). We identified a novel c.893G>A (p.Arg298Gln) mutation in the HOXD13 homeodomain. And the mutation affected the transcriptional activation ability of HOXD13.
Conclusion: This finding expands the phenotypic spectrum associated with HOXD13 mutations and advances our understanding of human limb development.
(Copyright © 2012. Published by Elsevier B.V.)