Novel mutation in the TCOF1 gene in a patient with Treacher Collins syndrome

AbstractTreacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development. The syndrome is characterized by a similar phenotype: micrognathia, microtia, midface hypoplasia, cleft lip and palate. The estimated incidence rate is 1/50000 live births. Treacher Collins syndrome is mostly caused by mutations in the TCOF1 gene, which encodes the serine/alanine-rich protein Treacle. TCS can also be caused by mutations in the POLR1C and POLR1D genes. About 70% of recognized mutations of the TCOF1 gene in TCS patients are deletions, which lead to formation of a termination codon and shortening of the protein. The aim of the study was to search for mutations in TCOF1 gene causing a Treacher Collins syndrome. Examined DNA was isolated from peripheral blood leukocytes of the male patient born at 38 weeks of gestation and his healthy parents. The PCR products were subjected to MSSCP analysis. The PCR products were purified on the DNA GelOut columns followed by direct sequencing. A novel, heterozygous deletion c.1978delC was detected in one patient with typical facial symptoms of Treacher Collins syndrome. The patient's parents were tested and no mutation was observed, indicating de novo origin of the examined mutation. The c.1978delC deletion causes premature termination of translation at 677aa. The finding will facilitate precise diagnosis of the patient and will extend knowledge on the pathogenesis of TCS