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Mutations in SOX10, a transcription modulator crucial in the development of the enteric nervous system (ENS), melanocytes and glial cells, are found in Shah-Waardenburg syndrome (WS4), a neurocristopathy that associates intestinal aganglionosis, pigmentation defects and sensorineural deafness. Expression of MITF and RET, two genes that play important roles(More)
When a sequence variation is found in a candidate gene for a disease, it is important to establish whether this change is neutral or responsible for the observed disorders in a patient. To answer this question, in the absence of further experimental investigations, several simulation programs have been proposed to predict whether a nonsynonymous(More)
ZFHX1B encodes Smad-interacting protein 1, a transcriptional corepressor involved in the transforming growth factors beta (TGFbeta) signaling pathway. ZFHX1B mutations cause a complex developmental phenotype characterized by severe mental retardation (MR) and multiple congenital defects. We compared the distribution of ZFHX1B transcripts during mouse and(More)
We identified a large Charcot-Marie-Tooth disease family with a novel mutation in the Connexin 32 (Cx32) P2 promoter region at position -526bp. This mutation was in a highly conserved SOX10 binding site. Functional studies were conducted on the Cx32 promoter that showed that this mutation reduced the activity of the Cx32 promoter and the affinity for SOX10(More)
Following complete optic nerve injury in a lizard, Ctenophorus ornatus, retinal ganglion cell (RGC) axons regenerate but fail to restore retinotectal topography unless animals are trained on a visual task (Beazley et al. [ 1997] J Comp Neurol 370:105-120, [2003] J Neurotrauma 20:1263-1270). Here we show that incomplete injury, which leaves some RGC axons(More)
Transcription factor SOX10 plays a role in the maintenance of progenitor cell multipotency, lineage specification, and cell differentiation and is a major actor in the development of the neural crest. It has been implicated in Waardenburg syndrome (WS), a rare disorder characterized by the association between pigmentation abnormalities and deafness, but(More)
We describe the case of a girl with an unusual congenital phenotype, combining peculiar peripheral nerve lesions with hypomyelination, chronic intestinal pseudoobstruction, and deafness. She was found to have a de novo heterozygous frameshift mutation in the gene encoding the SOX10 transcription factor. The likely role of SOX10 in determining the fate of(More)
The involvement of SOX10 and ZFHX1B in Waardenburg-Hirschsprung disease (hypopigmentation, deafness, and absence of enteric ganglia) and Mowat-Wilson syndrome (mental retardation, facial dysmorphy and variable congenital malformations including Hirschsprung disease) respectively, highlighted the importance of both transcription factors during enteric(More)
Approximately 30% of alleles causing genetic disorders generate premature termination codons (PTCs), which are usually associated with severe phenotypes. However, bypassing the deleterious stop codon can lead to a mild disease outcome. Splicing at NAGNAG tandem splice sites has been reported to result in insertion or deletion (indel) of three nucleotides.(More)