Background Brachydactyly type A2 (BDA2) is an autosomal dominant disorder. It was recently reported that a 5.9 kb duplication and a 5.5 kb duplication in the region 20p12.2–12.3 are associated with BDA2 in two European families.
Objective To characterise a 6-generation Chinese family with 16 members affected by BDA2 and map the gene to 20p12.2–12.3.
Methods and results A 4.6 kb duplication downstream of the bone morphogenetic protein 2 (BMP2) was identified in the family. The duplication co-segregated with the phenotype and was absent in unaffected family members and control subjects. Coding and splice-site mutations of all annotated genes in the critical region were also excluded. The duplication partially overlaps with the reported duplications but has a different breakpoint. The most conserved 2.1 kb fragment in the duplication was cloned into the pGL3-promoter vector downstream of the firefly luciferase reporter gene in the 5′ to 3′ orientation and transfected into osteosarcoma U-2OS and Hela cells. A reduced luciferase activity was observed.
Conclusion The smallest duplication is described, which partially overlaps the reported duplications but has a different breakpoint, and its association with BDA2 in a Chinese family is confirmed. The results also provide evidence for cis-regulatory sequences in the duplication 3′ of BMP2.
- copy number variation
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PS and HD contributed equally to this work.
Funding This work was supported by the State 985 Project, the National Natural Science Foundation of China (30700456).
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the ethics committee of the Sun Yat-Sen University for Human Study.
Provenance and peer review Not commissioned; externally peer reviewed.