Novel TBX5 Duplication in a Japanese Family with Holt-Oram Syndrome.

[holt-oram syndrome]

Holt-Oram syndrome is an autosomal dominant disorder characterized by upper limb malformations in the preaxial radial ray and cardiac septation and /or a conduction abnormality . It has been demonstrated that Holt-Oram syndrome is caused by mutations in the T -box transcription factor gene TBX 5 . Numerous germline mutations (more than 90 ) of this gene have been reported ; however , TBX 5 mutations are only identified in up to 74 Â % of typical Holt-Oram syndrome patients . We report a Japanese family with 2 affected individuals with the typical Holt-Oram syndrome phenotype , namely bilateral asymmetrical radial ray deformities and an atrial septal defect . An array-based comparative genomic hybridization study revealed an 11 -kb duplication at 12 q 24 .1 . Moreover , a multiplex ligation-dependent probe amplification study confirmed the duplication of exons 1 -6 of TBX 5 . Although a small duplication in TBX 5 (6 bases ) has been reported , a large duplication of this gene has not been described previously in typical Holt-Oram syndrome patients . All typical Holt-Oram syndrome cases in which a mutation is not identified should be screened for TBX 5 exon duplications .