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.

Identification of two novel mutations in the NOG gene associated with congenital stapes ankylosis and symphalangism

“…Such negative molecular data for family 3 indicate that there may be further genetic heterogeneity underlying SYNS1, with the involvement of at least one additional gene. In fact, two studies by Dawson et al 12 and van den Ende et al 26 found no mutations in either NOG or GDF5 in the patient with NOG-SSD. Moreover, they did not find any mutations in NOG, BMPR1B, GDF5 or FGF9 in a patient with a clinical phenotype showing features of SYNS1 or facioaudiosymphalangism, suggesting further genetic heterogeneity for these syndromes.…”