Alternative titles; symbols
ORPHA: 861; DO: 0080791;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 6p21.1 | Treacher Collins syndrome 3 | 248390 | Autosomal recessive | 3 | POLR1C | 610060 |
A number sign (#) is used with this entry because Treacher Collins syndrome-3 (TCS3) is caused by compound heterozygous mutation in the POLR1C gene (610060) on chromosome 6p21.
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).
Richieri-Costa et al. (1993) and Splendore et al. (2000) both reported sibs with Treacher Collins syndrome who were born to normal parents. The possibility of either nonpenetrance or germline mosaicism in one of the parents could not be discarded.
Treacher Collins syndrome-3 is an autosomal recessive disorder (Dauwerse et al., 2011).
Dauwerse et al. (2011) analyzed the POLR1C gene in 252 individuals with Treacher Collins syndrome and identified 3 patients, including 1 from a family previously studied by Splendore et al. (2000), with compound heterozygous mutations (610060.0001-610060.0005, respectively).
Dauwerse, J. G., Dixon, J., Seland, S., Ruivenkamp, C. A. L., van Haeringen, A., Hoefsloot, L. H., Peters, D. J. M., Clement-de Boers, A., Daumer-Haas, C., Maiwald, R., Zweier, C., Kerr, B., Cobo, A. M., Toral, J. F., Hoogeboom, A. J. M., Lohmann, D. R., Hehr, U., Dixon, M. J., Breuning, M. H., Wieczorek, D. Mutations in gene encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome. Nature Genet. 43: 20-22, 2011. [PubMed: 21131976] [Full Text: https://doi.org/10.1038/ng.724]
Richieri-Costa, A., Bortolozo, M. A., Lauris, J. R. P., Lauris, R. C. M. C., Guion-Almeida, M. L., Marques, D., Moreti, D. Mandibulofacial dysostosis: report on two Brazilian families suggesting autosomal recessive inheritance. Am. J. Med. Genet. 46: 659-664, 1993. [PubMed: 8362908] [Full Text: https://doi.org/10.1002/ajmg.1320460611]
Splendore, A., Silva, E. O., Alonso, L. G., Richieri-Costa, A., Alonso, N., Rosa, A., Carakushanky, G., Cavalcanti, D. P., Brunoni, D., Passos-Bueno, M. R. High mutation detection rate in TCOF1 among Treacher Collins syndrome patients reveals clustering of mutations and 16 novel pathogenic changes. Hum. Mutat. 16: 315-322, 2000. [PubMed: 11013442] [Full Text: https://doi.org/10.1002/1098-1004(200010)16:4<315::AID-HUMU4>3.0.CO;2-H]