A 4.6 kb genomic duplication on 20p12.2-12.3 is associated with brachydactyly type A2 in a Chinese family.
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Su P, Ding H, Huang D, Zhou Y, Huang W, Zhong L, Vyse TJ, Wang Y
A 4.6 kb genomic duplication on 20p12.2-12.3 is associated with brachydactyly type A2 in a Chinese family.
J Med Genet. 2011 May;48(5):312-6. doi: 10.1136/jmg.2010.084814. Epub 2011 Feb 26.
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- 21357617 [ View in PubMed]
- Abstract
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.