Mutation analysis ofTCOF1gene in Chinese Treacher Collins syndrome patients

Background Treacher Collins syndrome (TCS) is a rare autosomal dominant or recessive disorder, that involves unique bilateral craniofacial malformations. The phenotypes of TCS are extremely diverse. Interventional surgery can improve hearing loss and facial deformity in TCS patients. Method We recruited seven TCS families. Variant screening in probands was performed by targeted next-generation sequencing (NGS). The variants identified were confirmed by Sanger sequencing. The pathogenicity of all the mutations was evaluated using the guidelines of the American College of Medical Genetics and Genomics (ACMG) and InterVar software. Results Three frameshift variants, two nonsense variants, one missense variant, and one splicing variant ofTCOF1were identified in the seven TCS probands. Five variants including c.1393C > T, c.4111 + 5G>C, c.1142delC, c.2285_2286delCT, and c.1719delG had not been previously reported. Furthermore, we report the c.149A > G variant for the first time in a Chinese TCS patient. We provided prenatal diagnosis for family 4. Proband 7 chose interventional surgery. Conclusion We identified five novel variants inTCOF1in Chinese patients with TCS, which expands the mutation spectrum ofTCOF1in TCS. Bone conduction hearing rehabilitation can improve hearing for TCS patients and prenatal diagnosis can provide fertility guidance for TCS families.

Automated summary

Treacher Collins syndrome (TCS) is a rare genetic disorder with diverse symptoms. Using targeted next-generation sequencing can identify gene mutations in TCS patients, offering new diagnostic and genetic research insights. Interventional surgery can help improve hearing and facial deformities in TCS patients.