A PROPOSED NEW CONTIGUOUS GENE SYNDROME ON 8Q CONSISTS OF BRANCHIOOTORENAL (BOR) SYNDROME, DUANE SYNDROME, A DOMINANT FORM OF HYDROCEPHALUSAND TRAPEZE APLASIA - IMPLICATIONS FOR THE MAPPING OF THE BOR GENE

The analysis of a de novo 8q12.2 - q21.2 deletion led to the identific ation of a proposed previously undescribed contiguous gene syndrome co nsisting of Branchio-Oto-Renal (BOR) syndrome, Duane syndrome, hydroce phalus and trapeze aplasia. This is the first reported localization of the genes responsible for Duane syndrome and this dominant form of hy drocephalus. In contrast, we report a new localization for the gene re sponsible for BOR syndrome which is more telomeric to an initial place ment. Linkage analysis of affected families consistently mapped the ge ne responsible for BOR and Branchio-Oto (BO) syndromes to within the d eletion. Using new algorithms, a YAC contig was constructed and used t o localize the breakpoint of another chromosomal rearrangement associa ted with BO syndrome to a 500 kb interval within the deletion. The 8q1 2.2-q21.2 deletion suggests that reduced dosage of the relevant genes is sufficient to cause Duane syndrome, BOR syndrome and this dominant form of hydrocephalus.