title: Novel TBX5 duplication in a Japanese family with Holt-Oram syndrome.
abstract: 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 TBX5. Numerous germline mutations (more than 90) of this gene have been reported; however, TBX5 mutations are only identified in up to 74% 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 12q24.1. Moreover, a multiplex ligation-dependent probe amplification study confirmed the duplication of exons 1-6 of TBX5. Although a small duplication in TBX5 (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 TBX5 exon duplications.
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, 1-1 Seiryocho, Aoba-ku, Sendai, Miyagi, 980-8574, Japan, mkimura774@med.tohoku.ac.jp.
authors.forename: Masato
authors.initials: M
authors.lastname: Kimura
authors.forename: Atsuo
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Natsuko
authors.initials: N
authors.lastname: Ichinoi
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002648:Child; D004562:Electrocardiography; D006330:Heart Defects, Congenital / Q000235:genetics*; D006344:Heart Septal Defects, Atrial / Q000235:genetics*; D006801:Humans; D007564:Japan; D038061:Lower Extremity Deformities, Congenital / Q000235:genetics*; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D020825:T-Box Domain Proteins / Q000235:genetics*; D038062:Upper Extremity Deformities, Congenital / Q000235:genetics*
chemical_list: D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5