How to cite this article: Wang X, Xiao F, Yang Q, Liang B, Tang Z, Jiang L, Zhu Q, Chang W, Jiang J, Jiang C, Ren X, Liu J-Y, Wang QK, Liu M. 2006. A novel mutation in GDF5 causes autosomal dominant symphalangism in two Chinese families. Am J Med Genet Part A 140A:1846–1853.
A novel mutation in GDF5 causes autosomal dominant symphalangism in two Chinese families†
Article first published online: 4 AUG 2006
Copyright © 2006 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 140A, Issue 17, pages 1846–1853, 1 September 2006
How to Cite
Wang, X., Xiao, F., Yang, Q., Liang, B., Tang, Z., Jiang, L., Zhu, Q., Chang, W., Jiang, J., Jiang, C., Ren, X., Liu, J.-Y., Wang, Q. K. and Liu, M. (2006), A novel mutation in GDF5 causes autosomal dominant symphalangism in two Chinese families. Am. J. Med. Genet., 140A: 1846–1853. doi: 10.1002/ajmg.a.31372
- Issue published online: 18 AUG 2006
- Article first published online: 4 AUG 2006
- Manuscript Accepted: 16 MAY 2006
- Manuscript Received: 18 JAN 2006
- Tenth “Five-Year” National Science and Technology Key Program of China. Grant Number: 2004BA720A
- National Natural Science Foundation of China. Grant Number: 30470982
- Chinese Ministry of Science and Technology National High Technology “863” Programs of China. Grant Number: 2002BA711A07
- TGF-β domain
Proximal symphalangism (SYM1) is an autosomal dominant disorder characterized by ankylosis of the proximal interphalangeal joints and fusion of carpal and tarsal bones. We identified and characterized two five-generation Chinese families with SYM1. The two families share some similarities (e.g., osseous fusion of interphalangeal joints of the 2–4 fingers) with SYM1 families with mutations in the NOG gene or the family with mutation R438L recently reported in the GDF5 gene (encoding a bone morphogenetic protein family member). However, they show some unique features including the absence of cuboid bone, the lack of shortness of the first and fifth metacarpal bones, and manifestation of flat feet. Genome-wide linkage analysis of the two families mapped the disease gene to marker D20S112 with a combined LOD score of 4.32. Mutational analysis revealed a novel E491K mutation in the GDF5 gene in both families. The mutation occurs at a highly conserved residue in the TGF-β domain of GDF5 and represents the second GDF5 mutation identified for SYM1 to date. The E491K mutation co-segregated with the affected individuals in the two families, and did not exist in unaffected family members or 200 normal controls. These results indicate that defects in GDF5 can cause SYM1 in the Chinese population, and expand the spectrum of clinical phenotypes associated with mutant GDF5. © 2006 Wiley-Liss, Inc.