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Novel TBX5 mutations in patients with Holt-Oram syndrome.
Clin Orthop Relat Res 2007; 462:20-6CO

Abstract

Holt-Oram syndrome (MIM #142900) is an autosomal-dominant disorder characterized by radial ray deformities of the upper limb associated with cardiac septation and/or conduction defects. The disorder is caused by mutations in the transcription factor TBX5. Several studies report a rather low detection rate (range, 22-35%) of TBX5 mutations in patients with a clinical suspicion of Holt-Oram syndrome. The low detection rate is attributed to clinical misdiagnosis and genetic heterogeneity. However, a detection rate up to 74% has been reported when strict inclusion criteria for Holt-Oram syndrome are applied before genetic testing. We performed mutational analysis in a cohort of 27 unrelated patients referred with a clinical diagnosis of Holt-Oram syndrome. Seven TBX5 mutations were detected by direct sequencing. The detection rate of TBX5 mutations in this co hort of patients was 25.9% but increased to 54% when the strict phenotypical criteria were applied. No mutations were found in patients who did not meet these strict phenotypical criteria. Interestingly, we were unable to identify a TBX5 mutation in six of 13 patients who did meet the strict criteria. This study confirms TBX5 genetic testing should be reserved for patients who fulfill the strict phenotypic criteria for Holt-Oram syndrome.

Authors+Show Affiliations

Department of Orthopaedics, University Hospital Pellenberg, Pellenberg, Belgium. philippe.debeer@uz.kuleuven.ac.beNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17534187

Citation

Debeer, Philippe, et al. "Novel TBX5 Mutations in Patients With Holt-Oram Syndrome." Clinical Orthopaedics and Related Research, vol. 462, 2007, pp. 20-6.
Debeer P, Race V, Gewillig M, et al. Novel TBX5 mutations in patients with Holt-Oram syndrome. Clin Orthop Relat Res. 2007;462:20-6.
Debeer, P., Race, V., Gewillig, M., Devriendt, K., & Frijns, J. P. (2007). Novel TBX5 mutations in patients with Holt-Oram syndrome. Clinical Orthopaedics and Related Research, 462, pp. 20-6.
Debeer P, et al. Novel TBX5 Mutations in Patients With Holt-Oram Syndrome. Clin Orthop Relat Res. 2007;462:20-6. PubMed PMID: 17534187.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel TBX5 mutations in patients with Holt-Oram syndrome. AU - Debeer,Philippe, AU - Race,Valerie, AU - Gewillig,Marc, AU - Devriendt,Koen, AU - Frijns,Jean-Pierre, PY - 2007/5/31/pubmed PY - 2007/11/2/medline PY - 2007/5/31/entrez SP - 20 EP - 6 JF - Clinical orthopaedics and related research JO - Clin. Orthop. Relat. Res. VL - 462 N2 - Holt-Oram syndrome (MIM #142900) is an autosomal-dominant disorder characterized by radial ray deformities of the upper limb associated with cardiac septation and/or conduction defects. The disorder is caused by mutations in the transcription factor TBX5. Several studies report a rather low detection rate (range, 22-35%) of TBX5 mutations in patients with a clinical suspicion of Holt-Oram syndrome. The low detection rate is attributed to clinical misdiagnosis and genetic heterogeneity. However, a detection rate up to 74% has been reported when strict inclusion criteria for Holt-Oram syndrome are applied before genetic testing. We performed mutational analysis in a cohort of 27 unrelated patients referred with a clinical diagnosis of Holt-Oram syndrome. Seven TBX5 mutations were detected by direct sequencing. The detection rate of TBX5 mutations in this co hort of patients was 25.9% but increased to 54% when the strict phenotypical criteria were applied. No mutations were found in patients who did not meet these strict phenotypical criteria. Interestingly, we were unable to identify a TBX5 mutation in six of 13 patients who did meet the strict criteria. This study confirms TBX5 genetic testing should be reserved for patients who fulfill the strict phenotypic criteria for Holt-Oram syndrome. SN - 0009-921X UR - https://www.unboundmedicine.com/medline/citation/17534187/Novel_TBX5_mutations_in_patients_with_Holt_Oram_syndrome_ L2 - http://Insights.ovid.com/pubmed?pmid=17534187 DB - PRIME DP - Unbound Medicine ER -