TBX5 genetic testing validates strict clinical criteria for Holt-Oram syndrome

Deborah A. Mcdermott, Michael C. Bressan, Jie He, Joseph S. Lee, Salim Aftimos, Martina Brueckner, Fred Gilbert, Gail E. Graham, Mark C. Hannibal, Jeffrey W. Innis, Mary Ella Pierpont, Annick Raas-Rothschild, Alan L. Shanske, Wendy E. Smith, Robert H. Spencer, Martin G. St. John-Sutton, Lionel Van Maldergem, Darrel J. Waggoner, Matthew Weber, Craig T. Basson

Research output: Contribution to journalArticlepeer-review

108 Scopus citations


Holt-Oram syndrome (HOS) is an autosomal dominant hearthand syndrome characterized by congenital heart disease (CHD) and upper limb deformity, and caused by mutations in the TBX5 gene. To date, the sensitivity of TBX5 genetic testing for HOS has been unclear. We now report mutational analyses of a nongenetically selected population of 54 unrelated individuals who were consecutively referred to our center with a clinical diagnosis of HOS. TBX5 mutational analyses were performed in all individuals, and clinical histories and findings were reviewed for each patient without reference to the genotypes. Twenty-six percent of the complete cohort was shown to have mutations of the TBX5 gene. However, among those subjects for whom clinical review demonstrated that their presentations met strict diagnostic criteria for HOS, TBX5 mutations were identified in 74%. No mutations were identified in those subjects who did not meet these criteria. Thus, these studies validate our clinical diagnostic criteria for HOS including an absolute requirement for preaxial radial ray upper limb malformation. Accordingly, TBX5 genotyping has high sensitivity and specificity for HOS if stringent diagnostic criteria are used in assigning the clinical diagnosis.

Original languageEnglish
Pages (from-to)981-986
Number of pages6
JournalPediatric Research
Issue number5
StatePublished - Nov 2005
Externally publishedYes


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