Treacher Collins syndrome is a disorder of craniofacial development characterized by a combination of bilateral downward slanting of the palpebral fissures, colobomas of the lower eyelids with a paucity of eyelashes medial to the defect, hypoplasia of the ... Treacher Collins syndrome is a disorder of craniofacial development characterized by a combination of bilateral downward slanting of the palpebral fissures, colobomas of the lower eyelids with a paucity of eyelashes medial to the defect, hypoplasia of the facial bones, cleft palate, malformation of the external ears, atresia of the external auditory canals, and bilateral conductive hearing loss (Dauwerse et al., 2011). For additional phenotypic information and a discussion of genetic heterogeneity of Treacher Collins syndrome, see TCS1 (154500).
In a 3-year-old boy with Treacher Collins syndrome who was negative for mutation in the TCOF1 gene (606847), Dauwerse et al. (2011) performed genomewide copy number analysis and identified a 156-kb de novo deletion at chromosome 13q12.2 that ... In a 3-year-old boy with Treacher Collins syndrome who was negative for mutation in the TCOF1 gene (606847), Dauwerse et al. (2011) performed genomewide copy number analysis and identified a 156-kb de novo deletion at chromosome 13q12.2 that encompassed the entire POLR1D gene (613715) and exon 1 of the LNX2 gene (609733). Sequence analysis of POLR1D and LNX2 in 10 additional Treacher Collins patients who were negative for mutations in TCOF1 revealed a boy who was heterozygous for a nonsense mutation in POLR1D (R87X; 613715.0001). Analysis of POLR1D in a further 242 individuals with typical TCS or with clinical findings in the TCS phenotypic spectrum who were negative for TCOF1 mutations yielded 10 heterozygous nonsense mutations and 7 heterozygous missense mutations in 20 index cases (see, e.g., 613715.0002-613715.0006).