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Molecular basis of the clinical features of Holt-Oram syndrome resulting from missense and extended protein mutations of the TBX5 gene as well as TBX5 intragenic duplications.

Gene 2015 April 16
This paper reviews the molecular basis of the clinical features of Holt-Oram syndrome resulting from missense and extended protein mutations of the TBX5 gene as well as TBX5 intragenic duplications. First, we review all previously reported cases with these mutations, and then describe the pathogenesis of the clinical features in the heart and upper limb. Special emphasis is given to 'non-classic' upper limb features which are known to occur with these mutations. Finally, the molecular basis of other concurrent anomalies (chest wall, craniofacial, vertebral, and lung anomalies) is reviewed.

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