MAPPING THE TREACHER COLLINS SYNDROME LOCUS

Treacher Collins syndrome is an autosomal dominant condition characterized by bilateral craniofacial abnormalities. Clinical findings include malar hypoplasia, downslanting palpebral fissures, lower lid coloboma, and dysplastic ears. A sporadic case with the characteristic anomalies of this condition and a de novo, interstitial deletion of the short arm of chromosome 4 (46,XY,del(4)(pter->p15.2::p14->qter)) has recently been found. We plan to utilize this deletion to map the locus responsible for the Treacher Collins syndrome by using the following experimental approach: (1) Unrelated, affected individuals will be screened for microscopic, chromosome 4p deletions and other chromosomal abnormalities. (2) Linkage analysis in multigeneration, Treacher Collins families will be performed using polymorphic DNA markers that map to the chromosome 4p region. This analysis will determine if the gene defect responsible for this condition maps to chromosome 4p. (3) If we do not detect linkage between the disease and DNA markers from chromosome 4p, candidate genes and anonymous DNA markers will be used to map the gene defect for Treacher Collins syndrome. Mapping the gene responsible for this condition will be useful for diagnosis and genetic counseling and may lead to the cloning of the gene defect responsible for Treacher Collins syndrome.