title: Negative mutation screening of the NOG, BMPR1B, GDF5, and FGF9 genes indicates further genetic heterogeneity of the facioaudiosymphalangism syndrome.
abstract: We report on a patient with a clinical phenotype showing all the features of the multiple synostoses syndrome or the facioaudiosymphalangism syndrome, including symphalangism, condunction deafness, and the typical facies. Previously, it was shown that this condition is genetically heterogeneous with initially mutations described in the NOG gene, coding for Noggin, an extracellular antagonist of bone morphogenetic proteins. Noggin also interacts with growth differentiation factor 5 (GDF5), in which mutations have also been described in families with symphalangism. The latter is also the case for the BMP receptor BMPR1B to which GDF5 binds. Finally, a mutation in another growth factor, fibroblast growth factor 9, was found in a family with multiple synostoses syndrome. In our patient, we could, however, not show a causative mutation in any of these genes, providing evidence for further genetic heterogeneity of this syndrome.
authors.affiliation: Department of Medical Genetics, University Hospital Antwerp, University of Antwerp, Antwerp, Belgium. jenneke.vandenende@ua.ac.be
authors.forename: Jenneke J
authors.initials: JJ
authors.lastname: van den Ende
authors.forename: Vere
authors.initials: V
authors.lastname: Borra
authors.forename: Wim
authors.initials: W
authors.lastname: Van Hul
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000293:Adolescent; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics; D059327:Brachydactyly / Q000235:genetics* / Q000473:pathology; D002348:Carpal Bones / Q000002:abnormalities; D002352:Carrier Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D051525:Fibroblast Growth Factor 9 / Q000235:genetics; D005532:Foot Deformities, Congenital; D018740:Genetic Heterogeneity; D005820:Genetic Testing / Q000379:methods; D015894:Genome, Human; D055428:Growth Differentiation Factor 5 / Q000235:genetics; D006228:Hand Deformities, Congenital; D034381:Hearing Loss / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D013199:Stapes / Q000002:abnormalities; D013580:Synostosis / Q000235:genetics* / Q000473:pathology; D013639:Tarsal Bones / Q000002:abnormalities; D000099176:Noggin Protein
chemical_list: D052005:Bone Morphogenetic Protein Receptors, Type I; D002352:Carrier Proteins; D051525:Fibroblast Growth Factor 9; D055428:Growth Differentiation Factor 5; D000099176:Noggin Protein; C496459:FGF9 protein, human; C525893:GDF5 protein, human; C498214:BMPR1B protein, human