MOLECULAR CHARACTERIZATION OF PATIENTS WITH 18Q23 DELETIONS

The 18q(-) syndrome is a deletion syndrome that is characterized by me ntal retardation, hearing loss, midfacial hypoplasia, growth deficienc y, and limb anomalies. Most patients with this syndrome have deletions from 18q21-qter. We report: on three patients with deletions of 18q23 . A mother and daughter with identical deletions of 18q23 have many of the typical features of the 18q(-) syndrome, including midfacial hypo plasia and hearing loss. In contrast, the third patient has few of the symptoms of the 18q(-) syndrome. A contig of the 18q23 region was gen erated to aid in the mapping of the breakpoints. FISH was used to map both breakpoints to the same YAC clone. Furthermore, somatic-cell hybr ids from the daughter and the third patient were isolated. The mapping results of sequence-tagged sites relative to the two breakpoints were identical, suggesting that the two deletion breakpoints map very clos e to one another. The analyses of these patients demonstrate that the critical region for the 18q(-) syndrome maps to 18q23 but that a delet ion of 18q23 does not always lead to the clinical features associated with the syndrome. These patients demonstrate the wide phenotypic vari ability associated with deletions of 18q.