A splice donor site mutation in HOXD13 underlies synpolydactyly with cortical bone thinning

• We identified a splice donor site mutation c.781+1G > A.
• c.781+1G > A mutation activated a cryptic splice site and led to truncated protein.
• Truncated protein HOXD13MUT could not bind to EphA7 promoter.

Synpolydactyly 1(SPD1) is a dominantly inherited distal limb anomaly that is characterized by incomplete digit separation and increased number of digits. SPD1 is most commonly caused by polyalanine repeat expansions and mutations in the homeodomain of the HOXD13. We report a splice donor site mutation in HOXD13 associated in most cases with cortical bone thinning. In vitro study of transcripts and truncated protein analysis indicated that c.781+1G > A mutation results in truncated HOXD13 protein p.G190fsX4. Luciferase assay indicated that the truncated HOXD13 protein failed to bind to DNA. The mechanism for this phenotype was truncated protein loss of function.

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