Clinical and molecular study of Egyptian patients with Treacher Collins syndrome.

Treacher Collins syndrome (TCS) is a rare disorder of craniofacial development following different patterns of inheritance. To date, mutations in four genes (TCOF1, POLR1D, POLR1C, and POLR1B) have been found to cause the condition. The molecular defect remains unidentified in a significant proportion of patients. In the current study, whole exome sequencing including analysis of copy number variants was applied for genetic testing of eight Egyptian patients with typical TCS phenotype, representing the first molecular analysis of TCS patients in Egypt as well as in Arab countries. Five heterozygous frameshift mutations were reported, including four variants in the TCOF1 gene (c.3676_3694delinsCTCTGG, c.3984_3985delGA, c.4366_4369delGAAA, and c.3388delC) and one variant in the POLR1D gene (c.60dupA). Four variants were novel extending the disease mutation spectrum. In three affected individuals, no variants of interest were identified in genes associated with TCS or clinically overlapping conditions. Additionally, no relevant variant was detected in genes encoding other subunits of RNA polymerase (pol) I. Molecular analysis is important to provide accurate genetic counseling. It would also contribute to reduced disease incidence. Further studies should be designed to investigate other possible etiologies when no pathogenic variants were revealed in either of the known genes.