GENETIC BASIS OF OCULOAURICULAR VERTEBRAL DYSPLASIA

Oculoauriculovertebral vertebral dysplasia (OAV) has been suggested as a term to describe individuals with microtia, mandibular hypoplasia, vertebral anomalies and epibulbar dermoids or lipodermoids (Gorlin, R., et al., 1963). Phenotypes included under the OAV designation thus include hemifacial microsomia (HFM), and Goldenhar syndrome (GS). It has been suggested that these entities represent a single disorder with variable expression, and, that an isolated ear malformation may represent the mildest expression of this disorder. To date, while diagnostic criteria have not been meticulously defined for OAV, many individuals affected with OAV have ear malformations. Recent data has suggested that if specific criteria are used to ascertain affected probands with OAV, and careful physical examinations are performed on family members of affected OAV probands, OAV may be inherited in an autosomal dominant manner in at least some families. The goal of the studies described in this application is to identify the genetic basis of autosomal dominant OAV by: 1. Ascertaining families where OAV appears to be inherited in an autosomal dominant manner. 2. Identifying, using linkage analysis of the above listed families, a locus (or loci) for autosomal dominant human OAV. 3. Identifying, by physical mapping and positional cloning, candidate genes for OAV in the locus (or loci) identified in Aim 2.