DESCRIPTION (provided by applicant): Kabuki syndrome (KS) is a multiple congenital anomaly/mental retardation syndrome that heretofore has had an unknown etiology. Although several cases with KS features have been reported with different chromosome anomalies, none have had an autosomal cytogenetic aberration in common. Our preliminary data have demonstrated an 8p22-8p23.1 duplication using comparative genomic hybridization in 6 unrelated patients diagnosed with KS. BAC-FISH analysis in all cases confirmed these observations and delimited the duplicated region to approximately 3.5 Mb. We aim to refine the KS critical region using BAC-FISH probes and DNA sequencing, discover potential molecular pathways using microarray expression experiments, and investigate potential genotype/phenotype correlations with different sized duplications or other types of mutations leading to KS. Further investigation into the etiology of KS and related phenotypes with identification of specific responsible genes will increase our understanding of human growth, mental development, and hearing loss.