De novo TCOF1 mutation in Treacher Collins syndrome.

OBJECTIVE

To analyze the genetic cause of a hearing loss child with the Treacher Collins syndrome (TCS) phenotypes of malar hypoplasia, micrognathia, antimongoloid slanting palpebral fissures and cup ears.

METHODS

Clinical analysis, hearing tests, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) were performed on the family members.

RESULTS

The 6 months old boy with a range of Treacher Collins syndrome phenotypes including malar hypoplasia, micrognathia, antimongoloid slanting palpebral fissures, cup ears, and hearing loss. While CMA analyses did not detect significant deletion or duplication, WES analysis identified a novel nonsense mutation c.163C > T (p.Q55X) in exon 2 of TCOF1 gene. Sanger sequencing analysis confirmed the mutation in the patient, but not in his parents.

CONCLUSION

This article reports a novel nonsense mutation located at exon 2 in TCOF1 gene, which predicts premature protein termination of treacle, indicating that haploinsufficiency of TCOF1 gene is responsible for Treacher Collins syndrome. Our study increases the cohort of Chinese TCS patients, and expands the TCS variation spectrum.