| Autor: |
Everman, David B., Bartels, Cynthia F., Yang, Yue, Yanamandra, Niranjan, Goodman, Frances R., Mendoza-Londono, J. Roberto, Savarirayan, Ravi, White, Susan M., Graham, John M., Gale, Robert Peter, Svarch, Eva, Newman, William G., Kleckers, Albert R., Francomano, Clair A., Govindaiah, Vinukonda, Singh, Lalji, Morrison, Stuart, Thomas, J. Terrig |
| Zdroj: |
American Journal of Medical Genetics. Part A; 15 October 2002, Vol. 112 Issue: 3 p291-296, 6p |
| Abstrakt: |
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 disulfide-linked dimers when expressed in vitro. These data support the hypothesis that BDC results from functional haploinsufficiency for GDF5. © 2002 Wiley-Liss, Inc. |
| Databáze: |
Supplemental Index |
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