Background: Brachydactyly type A2 (BDA2) is an autosomal dominant disease characterized by the deformation of the middle phalanx of the second fingers and toes. It has been reported to be associated with three genes regulating the osteogenesis, including BMPR1B, GDF5 and BMP2.
Materials and methods: 10 BDA2 patients and 7 unaffected individuals in a Chinese family were identified through clinical signs and radiographs. The mutation analyses of BMPR1B, GDF5 and BMP2 gene was performed in all the available family members and 100 control subjects. The duplication analysis for the downstream of BMP2 was also performed in all the samples.
Results: A novel 4671bp duplication downstream the BMP2 gene was identified in all the patients undergoing molecular analysis but not in the unaffected individuals and healthy controls, with a 28bp microhomology flanking it. There was no mutation in all the exons of BMPR1B, GDF5 and BMP2 in all the tested family members.
Conclusion: The novel duplication has different breakpoints compared with the previous ones but highly overlapped with them. The duplication narrows the range of the potential cis-regulatory sequence, and further supports the association between BDA2 and the duplication downstream BMP2.
Keywords: BMP2; Brachydactyly; Duplication; Microhomology; Molecular genetics.
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