A novel familial mutation associated with Treacher Collins syndrome: A case report.

ABSTRACT

Treacher Collins syndrome (TCS) is a type of mandibulofacial dysostosis with incomplete penetrance and high intra- and interfamilial clinical heterogeneity, and it is associated with mutations of treacle ribosome biogenesis factor 1 (TCOF1), and RNA polymerase I and III subunit (POLR1)C and POLR1D genes. In the present case report, a patient with TCS with auricle dysplasia and hearing loss accompanied with intellectual disability is described. Sequence analysis was performed on blood samples from the patient and his father via oligonucleotide-based target capture, followed by next-generation sequencing. Alignment and variant calls were generated using the Burrows-Wheeler Aligner and Genome Analysis Toolkit, followed by bioinformatics analysis of the detected variants. A novel heterozygous mutation, c.911C>T (p.Ser304Leu), was detected in the TCOF1 gene, which was inherited from the father. The father of the patient only suffered from hearing loss. The present report is the first to identify an association between phenotypic variability and TCOF1 gene mutations and thus contributes to our understanding of the association between the genotype and phenotype in patients with TCS and offers clinically relevant information for diagnosis of the syndrome.