A De Novo Mutation Destroys the Central Repeated Domain of TCOF1 in a Chinese Family with Treacher Collins Syndrome

Abstract

Abstract Treacher Collins syndrome (TCS, MIM #154500) is a severe congenital disorder implicated in particular dysplasia of the craniofacial bones, accompanied by downslanting palpebral fissures, lower eyelid colobomas, microtia, or other craniofacial malformations. However, the underlying pathogenic mutations in TCS are still unknown, and elucidating these is of primary importance for TCS researchers. We collected samples from a Chinese TCS family, including the proband and two parents. Sequencing, genotyping, and in silico analyses were employed to detect pathogenic mutations in the pedigree. In the proband, a de novo frameshift mutation of TCOF1 c.1562_1574del (p.A521fs) was identified as a pathogenic candidate, while the parents showed no mutations. The frameshift mutation results in TCOF1 truncation and damages the central repeat domain, which is the binding site for transcriptional factors. In conclusion, we identified a novel mutation TCOF1 c.1562_1574del, which is likely a pathogenic mutation for TCS, thereby expanding the mutation spectrum of TCS.