Transcriptional map of the Treacher Collins candidate gene region.

Abstract

Treacher Collins syndrome (TCOF1) is a dominant disorder of craniofacial development that has been linked previosuly to a region of chromosome 5q31.3-32. Identification of recombination events in affected individuals has reduced the candidate gene region to a 0.5-Mb area between the loci RPS14 (proximal) and ANX6 [distal]. A transcriptional map of this candidate gene region, generated by analysis of exon amplification clones, has identified the genomic location of four genes, heparan sulfate-N-sulfotransferase-N-deacetylase, glutathione peroxidase, as well as two novel, previously uncharacterized genes. Each of these genes, based on their location, must be considered candidates for TCOF1 locus.

Clinical spectrum of Treacher Collins syndrome

“…The first extensive review of the condition was detailed by Franceschetti and Klein, 1949, who used the term mandibulofacial dysostosis to describe its clinical features. 3 Symmetrical and bilateral involvement with clinical features like (1) abnormalities of the external ears, atresia of the external ear canals and malformation of the middle ear ossicles resulting in bilateral conductive hearing loss;…”

“…(2) lateral downward sloping of the palpebral fissures, frequently with coloboma of the lower eyelids; (3) hypoplasia of the mandible and zygomatic complex, and (4) presence of cleft palate in TCS. 3 These patients may present with chronic obstruction of the upper airways, micrognathia, tongue posture impairment, pharyngeal hypoplasia, laryngeal and tracheal narrowing with respiratory obstruction and obstructive sleep apnea syndrome. 1 Goldenhar syndrome, Nager's dysostosis and Miller's syndrome are among its differential diagnoses.…”

TCOF1 gene encodes a putative nucleolar phosphoprotein that exhibits mutations in Treacher Collins Syndrome throughout its coding region

“…This was then refined to the region between the colony stimulating factor 1 receptor gene (CSF1R) (proximally) and osteonectin gene (SPARC) (distally) (8,9), and subsequently further refined to between marker D5S519, which is distal to CSF1R and SPARC (10). Physical and transcription maps of these regions were constructed (11)(12)(13). A candidate gene for TCS was recently identified (14) which, confusingly, in light of previous studies (10,12) lies proximal to D5S519, between it and CSF1R.…”