The mutational spectrum of brachydactyly type C

David B. Everman, Cynthia F. Bartels, Yue Yang, Niranjan Yanamandra, Frances R. Goodman, J. Roberto Mendoza-Londono, Ravi Savarirayan, Susan M. White, John M. Graham, Robert Peter Gale, Eva Svarch, William G. Newman, Albert R. Kleckers, Clair A. Francomano, Vinukonda Govindaiah, Lalji Singh, Stuart Morrison, J. Terrig Thomas, Matthew L. Warman

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Growth/differentiation factor-5 (GDF5), also known as cartilage-derived morphogenetic protein-1 (CDMP-1), is a secreted signaling molecule that participates in skeletal morphogenesis. Heterozygous mutations in GDF5, which maps to human chromosome 20, occur in individuals with autosomal dominant brachydactyly type C (BDC). Here we show that BDC is locus homogeneous by reporting a GDF5 frameshift mutation segregating with the phenotype in a family whose trait was initially thought to map to human chromosome 12. We also describe heterozygous mutations in nine additional probands/families with BDC and show nonpenetrance in a mutation carrier. Finally, we show that mutant GDF5 polypeptides containing missense mutations in their active domains do not efficiently form disulfidelinked dimers when expressed in vitro. These data support the hypothesis that BDC results from functional haploinsufficiency for GDF5.

Original languageEnglish (US)
Pages (from-to)291-296
Number of pages6
JournalAmerican journal of medical genetics
Issue number3
StatePublished - Oct 15 2002
Externally publishedYes


  • Brachydactyly type C
  • Cartilage-derived morphogenetic protein 1
  • Growth/ differentiation factor 5

ASJC Scopus subject areas

  • Genetics(clinical)


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