Eri Arikawa-Hirasawa, M.D., Ph.d., is a neurologist, who worked at the National Institute of Dental and Craniofacial Research, National Institutes of Health for the past 5 years. She is now an assistant professor in the Department of Neurology at Juntendo University Medical School in Japan. Her major interest has been in muscle disorders and neural development. She was instrumental in creating knockout mice for perlecan and identifying the unexpected cartilage defects in the mutant mice, whose phenotype led to the identification of mutations in the perlecan gene of DDSH patients.
Dyssegmental dysplasia, Silverman-Handmaker type: Unexpected role of perlecan in cartilage development#
Version of Record online: 25 JAN 2002
Published 2002 Wiley-Liss, Inc.
American Journal of Medical Genetics
Special Issue: Latest Developments in Skeletal Dysplasias
Volume 106, Issue 4, pages 254–257, Winter 2001
How to Cite
Arikawa-Hirasawa, E., Wilcox, W. R. and Yamada, Y. (2001), Dyssegmental dysplasia, Silverman-Handmaker type: Unexpected role of perlecan in cartilage development. Am. J. Med. Genet., 106: 254–257. doi: 10.1002/ajmg.10229
This article was prepared by a group consisting of both United States Government employees and non-United States Government employees, and as such is subject to 117 U.S.C. Sec. 105.
- Issue online: 23 OCT 2002
- Version of Record online: 25 JAN 2002
- dyssegmental dysplasia;
- Silverman-Handmaker type (DDSH);
- functional null mutations;
- Schwartz-Jampel syndrome (SJS)
Dyssegmental dysplasia, Silverman-Handmaker type (DDSH), is a lethal autosomal recessive form of dwarfism with characteristic anisospondylic micromelia. The remarkable similarities in the radiographic, clinical, and chondroosseous morphology of DDSH patients to those of perlecan-null mice led to the identification of mutations in the perlecan gene (HSPG2) of DDSH. Perlecan, a large heparan sulfate proteoglycan, is expressed in various tissues and is a component of all basement membrane extracellular matrices. A chondrodysplasia phenotype caused by the loss of perlecan was unexpected, because cartilage does not have basement membranes. Insertion and splicing mutations in HSPG2 of DDSH were found that were predicted to create a premature termination codon. Immunostaining and biochemical analysis revealed that the mutant perlecan molecules were unstable and not secreted into the extracellular matrix. These results indicate that DDSH is caused by functional null mutations of HSPG2 and that perlecan is essential for cartilage development. Published 2002 Wiley-Liss, Inc.