title: A 4.6 kb genomic duplication on 20p12.2-12.3 is associated with brachydactyly type A2 in a Chinese family.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopedics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Peiqiang
authors.initials: P
authors.lastname: Su
authors.forename: Hongke
authors.initials: H
authors.lastname: Ding
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Weijun
authors.initials: W
authors.lastname: Huang
authors.forename: Liangying
authors.initials: L
authors.lastname: Zhong
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
mesh_terms: D001483:Base Sequence; D059327:Brachydactyly; D045744:Cell Line, Tumor; D019457:Chromosome Breakage; D058674:Chromosome Duplication / Q000235:genetics*; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D005260:Female; D005532:Foot Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics; D023061:Gene Order; D017930:Genes, Reporter / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006228:Hand Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D011859:Radiography