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.
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Authors | Masato Kimura, Atsuo Kikuchi, Natsuko Ichinoi, Shigeo Kure |
Journal | Pediatric cardiology
(Pediatr Cardiol)
Vol. 36
Issue 1
Pg. 244-7
(Jan 2015)
ISSN: 1432-1971 [Electronic] United States |
PMID | 25274398
(Publication Type: Case Reports, Journal Article)
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Chemical References |
- T-Box Domain Proteins
- T-box transcription factor 5
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Topics |
- Abnormalities, Multiple
(genetics)
- Child
- Electrocardiography
- Heart Defects, Congenital
(genetics)
- Heart Septal Defects, Atrial
(genetics)
- Humans
- Japan
- Lower Extremity Deformities, Congenital
(genetics)
- Male
- Pedigree
- Polymorphism, Single Nucleotide
- T-Box Domain Proteins
(genetics)
- Upper Extremity Deformities, Congenital
(genetics)
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