Unmasking Kabuki syndrome: chromosome 8p22-8p23.1 duplication revealed by comparative genomic hybridization and BAC-FISH

Kabuki syndrome (KS) is a multiple congenital anomalies/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. We found an 8p22-8p23.1 duplication, using comparative genomic hybridization (CGH) in six unrelated patients diagnosed with KS. This observation was confirmed using BAC-FISH in all cases that delimited the duplicated region to approximately 3.5 Mb. No duplication of this region was found in two parents or 20 controls by either CGH or BAC-FISH. Two out of two mothers of KS patients and one out of 20 controls were found to have a heterozygous submicroscopic inversion at 8p23.1. As the six patients with KS represent different races, this duplication may represent a common etiologic basis for this disorder.