Treacher Collins syndrome (TCS) (MIM 154500) is a disorder of craniofacial development that is inherited in an autosomal dominant fashion and occurs with an incidence of approximately 1 in 50,000 live births. Forty percent of patients have a previous family history, whereas in 60 percent of patients the syndrome is thought to arise as a result of a de novo mutation.
TCS is characterized by abnormalities of the external ears, conductive hearing loss, lateral downward sloping of the palpebral fissures, cleft palate, and hypoplasia of the mandible and zygomatic complex. These features often are bilaterally symmetrical in nature. A marked variation in phenotype is observed both within and between families.
In the absence of a candidate gene or appropriate mouse model for the disorder, the mutated gene causing TCS (TCOF1) was isolated by positional cloning strategies. So far, approximately 70, mainly family-specific, mutations have been identified within the gene, which maps to chromosome 5q32-q33.1. The majority of these mutations introduce a premature termination codon.
Since database sequence comparisons failed to reveal any strong homology, little was known about the precise function of the protein, treacle, encoded by TCOF1. Recent work on the expression of treacle suggests that it is a member of a family of nucleolar phosphoproteins and, as such, may be involved in shuttling proteins between the nucleus and the cytoplasm.