Treacher Collins-Franceschetti 1 syndrome is characterized by abnormal craniofacial development. Defects in the TCOF1 gene on chromosome 5 are the main cause of this disease. This gene encodes a nuclear protein with a LIS1 homology domain. The protein is involved in ribosomal DNA gene transcription through its interaction with upstream binding factor (UBF). The protein encoded by TCOF1 is treacle. This protein is active during early embryonic development in structures that become bones and other tissues in the face.
The TCOF1 gene (26 exons) spans ~43 kb of genomic DNA and is located on 5q33.1, about 150 Mb from the p-telomere. The P310-B3 probemix contains one probe for each exon of the gene with the exception of exons 8, 19 and 20. In addition, the probemix contains a probe for intron 6 and a probe for intron 16. This probemix furthermore contains ten reference probes, detecting ten different autosomal chromosomal locations.
This SALSA® MLPA® probemix is designed to detect deletions/duplications of one or more sequences in the aforementioned gene in a DNA sample. Heterozygous deletions of recognition sequences should give a 35-50% reduced relative peak height of the amplification product of that probe. Note that a mutation or polymorphism in the sequence detected by a probe can also cause a reduction in relative peak height, even when not located exactly on the ligation site! In addition, some probe signals are more sensitive to sample purity and small changes in experimental conditions. Therefore, deletions and duplications detected by MLPA should always be confirmed by other methods. Not all deletions and duplications detected by MLPA will be pathogenic; users should always verify the latest scientific literature when interpreting their findings. We have no information on what percentage of defects in these genes is caused by deletions/duplications of complete exons. Finally, note that most defects in this gene are expected to be small (point) mutations which will not be detected by this SALSA® MLPA® test.