[Analysis of pathogenic gene variant in two children with Treacher-Collins syndrome]

To explore the clinical and genetic characteristics of two children with a clinical diagnosis of Treacher Collins syndrome (TCS).

Whole-exome sequencing was used to screen potential variants in the two children. Confirmation of suspected variants was performed through Sanger sequencing, multiplex ligation dependent probe amplification and real-time PCR in probands and their parents.

A heterozygous deletion variant, c.4357_4360delGAAA, was detected in case one, while was de novo and verified by Sanger sequencing. The variant was classified as pathogenic (PVS1 +PM2+PM6) according to ACMG guideline. The heterozygous deletion of exon 1-7 was seen in the same gene in case 2, which MLPA verified as heterozygous deletion of exon 1-6. This deletion was inherited from the father with a normal phenotype, and the father's TCOF1 gene was suspected to be chimeric heterozygous deletion of exon 1-6 verified by MLPA.

The identified variants in the TCOF1 gene probably underlie the two cases of TCS. There was no apparent correlation between genotype and phenotype. In addition, it shows a high interfamilial variability ranging from normal to full presentation of TCS. Genetic detection provided clinical diagnosis and genetic counselling for TCS patients.