PT  - JOURNAL ARTICLE
AU  - Su, Peiqiang
AU  - Ding, Hongke
AU  - Huang, Dongsheng
AU  - Zhou, Yan
AU  - Huang, Weijun
AU  - Zhong, Liangying
AU  - Vyse, Tim J
AU  - Wang, Yiming
TI  - A 4.6 kb genomic duplication on 20p12.2–12.3 is associated with brachydactyly type A2 in a Chinese family
AID  - 10.1136/jmg.2010.084814
DP  - 2011 May 01
TA  - Journal of Medical Genetics
PG  - 312--316
VI  - 48
IP  - 5
4099  - http://jmg.bmj.com/content/48/5/312.short
4100  - http://jmg.bmj.com/content/48/5/312.full
SO  - J Med Genet2011 May 01; 48
AB  - 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.