A novel mutation outside homeodomain of HOXD13 causes synpolydactyly in a Chinese family.
BACKGROUND
Human synpolydactyly (SPD), belonging to syndactyly (SD) II, is caused by mutations in homeobox d13 (HOXD13). Here, we describe the study of a two-generation Chinese family with a variant form of synpolydactyly.


METHODS
The sequence of the HOXD13 gene was analyzed. Luciferase assays were conducted to determine whether the mutation affected the function of the HOXD13 protein.


RESULTS
We identified a novel c.659G>C (p.Gly220Ala) mutation outside the HOXD13 homeodomain responsible for the disease in this family. This mutation was not found in any of the unaffected family members and healthy control. Luciferase assays demonstrated that this mutation affected the transcriptional activation ability of HOXD13 (only approximately 84.7% of wild type, p<0.05).


CONCLUSIONS
Phenotypes displayed by individuals carrying the novel mutation present additional features, such as the fifth finger clinodactyly, which is not always associated with canonical SPD. This finding enhances our understanding about the phenotypic spectrum associated with HOXD13 mutations and advances our understanding of human limb development.
Department of Microsurgery and Orthopedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Xiang
X
Zhou
Canbin
C
Zheng
Bo
B
He
Zhaowei
Z
Zhu
Ping
P
Li
Xinhua
X
He
Shuang
S
Zhu
Chuan
C
Yang
Zhenguo
Z
Lao
Qingtang
Q
Zhu
Xiaolin
X
Liu
D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010375:Pedigree; D013576:Syndactyly / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
C513184:HOXD13 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors
Homeodomain; Hoxd13; Luciferase assays; Novel mutation; Synpolydactyly