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

Abstract

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.

• Authors: Xiuyan Shi, Chunyan Ji, Lihua Cao, Yuhong Wu, Yuyang Shang, Wei Wang, Yang Luo
• Journal: Gene (Gene) Vol. 532 Issue 2 Pg. 297-301 (Dec 15 2013) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 24055421 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Codon, Nonsense
• HOXD13 protein, human
• Homeodomain Proteins
• RNA Splice Sites
• Transcription Factors
• Receptor, EphA7

Topics

• Animals
• Base Sequence
• Bone Matrix (abnormalities)
• Codon, Nonsense
• DNA Mutational Analysis
• Genetic Association Studies
• Homeodomain Proteins (genetics, metabolism)
• Humans
• Mice
• NIH 3T3 Cells
• Pedigree
• Promoter Regions, Genetic
• Protein Binding
• RNA Splice Sites
• Receptor, EphA7 (genetics)
• Syndactyly (genetics)
• Transcription Factors (genetics, metabolism)
• Transcription, Genetic