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  GDF5 Is a Second Locus for Multiple-Synostosis Syndrome

Dawson, K., Seemann, P., Sebald, E., King, L., Edwards, M., Williams III, J., et al. (2006). GDF5 Is a Second Locus for Multiple-Synostosis Syndrome. American Journal of Human Genetics (Chicago, IL), 78(4), 708-712.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8458-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8459-7
Genre: Journal Article
Alternative Title : Am J Hum Genet

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 Creators:
Dawson, Katherine, Author
Seemann, Petra1, Author              
Sebald, Eiman, Author
King, Lily, Author
Edwards, Matthew, Author
Williams III, John, Author
Mundlos, Stefan1, Author              
Krakow, Deborah, Author
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              

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 Abstract: Multiple-synostosis syndrome is an autosomal dominant disorder characterized by progressive symphalangism, carpal/tarsal fusions, deafness, and mild facial dysmorphism. Heterozygosity for functional null mutations in the NOGGIN gene has been shown to be responsible for the disorder. However, in a cohort of six probands with multiple-synostosis syndrome, only one was found to be heterozygous for a NOGGIN mutation (W205X). Linkage studies involving the four-generation family of one of the mutation-negative patients excluded the NOGGIN locus, providing genetic evidence of locus heterogeneity. In this family, polymorphic markers flanking the GDF5 locus were found to cosegregate with the disease, and sequence analysis demonstrated that affected individuals in the family were heterozygous for a novel missense mutation that predicts an R438L substitution in the GDF5 protein. Unlike mutations that lead to haploinsufficiency for GDF5 and produce brachydactyly C, the protein encoded by the multiple-synostosis–syndrome allele was secreted as a mature GDF5 dimer. These data establish locus heterogeneity in multiple-synostosis syndrome and demonstrate that the disorder can result from mutations in either the NOGGIN or the GDF5 gene.

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Language(s): eng - English
 Dates: 2006-04
 Publication Status: Published in print
 Pages: -
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 Identifiers: eDoc: 313082
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Title: American Journal of Human Genetics (Chicago, IL)
  Alternative Title : Am J Hum Genet
Source Genre: Journal
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Pages: - Volume / Issue: 78 (4) Sequence Number: - Start / End Page: 708 - 712 Identifier: ISSN: 0002-9297