Treacher Collins Syndrome (TCS) is an autosomal dominant disorder ofcraniofacial development, the features of which include conductive hearing loss and cleft palate [, ]; it is the most common of the human mandibulo-facial dysostosis disorders []. The TCS locus has been mapped to human chromosome 5q31.3-32 and the mutated gene identified (TCOF1) []. To date, 35 mutations have been reported in TCOF1, all but one of which result in the introduction of a premature-termination codon into the predicted protein, Treacle. The observed mutational spectrum supports the hypothesis that TCS results from haploinsufficiency.Treacle is a low complexity protein of 1,411 amino acids whose predictedprotein structure contains a set of highly polar repeated motifs []. These motifs are common to nucleolar trafficking proteins in other species and are predicted to be phosphorylated by casein kinase. In concert with this observation, the full-length TCOF1 protein sequence also contains putative nuclear and nucleolar localisation signals []. Throughout the open reading frame are found mutations in TCS families and several polymorphisms. It has thus been suggested that TCS results from defects in a nucleolar trafficking protein that is critically required during human craniofacial development.This entry contains Treacle and other related proteins.
Treacher Collins Syndrome (TCS) is an autosomal dominant disorder ofcraniofacial development, the features of which include conductive hearing loss and cleft palate [, ]; it is the most common of the human mandibulo-facial dysostosis disorders []. The TCS locus has been mapped to human chromosome 5q31.3-32 and the mutated gene identified (TCOF1) []. To date, 35 mutations have been reported in TCOF1, all but one of which result in the introduction of a premature-termination codon into the predicted protein, Treacle. The observed mutational spectrum supports the hypothesis that TCS results from haploinsufficiency.Treacle is a low complexity protein of 1,411 amino acids whose predictedprotein structure contains a set of highly polar repeated motifs []. These motifs are common to nucleolar trafficking proteins in other species and are predicted to be phosphorylated by casein kinase. In concert with this observation, the full-length TCOF1 protein sequence also contains putative nuclear and nucleolar localisation signals []. Throughout the openreading frame are found mutations in TCS families and several polymorphisms. It has thus been suggested that TCS results from defects in a nucleolar trafficking protein that is critically required during human craniofacial development.
