RGD Reference Report - GDF5 is a second locus for multiple-synostosis syndrome. - Rat Genome Database

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GDF5 is a second locus for multiple-synostosis syndrome.

Authors: Dawson, Katherine  Seeman, Petra  Sebald, Eiman  King, Lily  Edwards, Matthew  Williams, John  Mundlos, Stephan  Krakow, Deborah 
Citation: Dawson K, etal., Am J Hum Genet. 2006 Apr;78(4):708-12. Epub 2006 Feb 24.
RGD ID: 12738199
Pubmed: PMID:16532400   (View Abstract at PubMed)
PMCID: PMC1424701   (View Article at PubMed Central)
DOI: DOI:10.1086/503204   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GDF5Humanmultiple synostoses syndrome 1  IAGP DNA:missense mutation:cds:p.R438L(1313G>T)(human)RGD 
Gdf5Ratmultiple synostoses syndrome 1  ISOGDF5 (Homo sapiens)DNA:missense mutation:cds:p.R438L(1313G>T)(human)RGD 
Gdf5Mousemultiple synostoses syndrome 1  ISOGDF5 (Homo sapiens)DNA:missense mutation:cds:p.R438L(1313G>T)(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gdf5  (growth differentiation factor 5)

Genes (Mus musculus)
Gdf5  (growth differentiation factor 5)

Genes (Homo sapiens)
GDF5  (growth differentiation factor 5)


Additional Information