van den Ende Jenneke J, Borra Vere, Van Hul Wim
Department of Medical Genetics, University Hospital Antwerp, University of Antwerp, Antwerp, Belgium.
Clin Dysmorphol. 2013 Jan;22(1):1-6. doi: 10.1097/MCD.0b013e3283590986.
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.
我们报告了一名患者，其临床表型显示出多关节融合综合征或面-听-指关节综合征的所有特征，包括指关节融合、传导性耳聋和典型面容。此前研究表明，这种疾病在遗传上具有异质性，最初在编码骨形态发生蛋白细胞外拮抗剂Noggin的NOG基因中发现了突变。Noggin还与生长分化因子5（GDF5）相互作用，在指关节融合家族中也发现了该因子的突变。GDF5所结合的骨形态发生蛋白受体BMPR1B也是如此。最后，在一个多关节融合综合征家族中发现了另一种生长因子——成纤维细胞生长因子9的突变。然而，在我们的患者中，我们未能在这些基因中的任何一个中发现致病突变，这为该综合征进一步的遗传异质性提供了证据。
