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The fibulin-1 gene (FBLN1) is disrupted in a t(12;22) associated with a complex type of synpolydactyly
  1. P Debeer1,2,*,
  2. E F P M Schoenmakers1,2,
  3. W O Twal3,
  4. W S Argraves3,
  5. L De Smet4,
  6. J-P Fryns1,
  7. W J M Van de Ven1,2
  1. 1Centre for Human Genetics, Herestraat 49, B-3000 Leuven, Belgium
  2. 2Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium
  3. 3Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, SC, USA
  4. 4Department of Orthopaedic Surgery, University Hospital Pellenberg, Weligerveld 1, B-3212 Pellenberg, Belgium
  1. Correspondence to:
 Dr P Debeer, Centre for Human Genetics, Herestraat 49, B-3000 Leuven, Belgium; 


Molecular analysis of the reciprocal chromosomal translocation t(12;22)(p11.2;q13.3) cosegregating with a complex type of synpolydactyly showed involvement of an alternatively spliced exon of the fibulin-1 gene (FBLN1 located in 22q13.3) and the C12orf2 (HoJ-1) gene on the short arm of chromosome 12. Investigation of the possible functional involvement of the fibulin-1 protein (FBLN1) in the observed phenotype showed that FBLN1 is expressed in the extracellular matrix (ECM) in association with the digits in the developing limb. Furthermore, fibroblasts derived from patients with the complex type of synpolydactyly displayed alterations in the level of FBLN1-D splice variant incorporated into the ECM and secreted into the conditioned culture medium. By contrast, the expression of the FBLN1-C splice variant was not perturbed in the patient fibroblasts. Based on these findings, we propose that the t(12;22) results in haploinsufficiency of the FBLN1-D variant, which could lead to the observed limb malformations.

  • synpolydactyly
  • fibulin-1
  • limb development
  • Approved gene symbols were obtained from the HUGO Nomenclature Committee: FBLN1 = human fibulin-1 gene
  • FBLN1 = human fibulin-1 protein
  • fbln1 = mouse fibulin-1 gene
  • fbln1 = mouse fibulin-1 protein
  • ECM, extracellular matrix

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  • * Present address: Department of Human Genetics, University Medical Centre Nijmegen, Nijmegen, The Netherlands