ArticleEuropean journal of human genetics : EJHG2012
TBX5 intragenic duplication: a family with an atypical Holt-Oram syndrome phenotype.
Article in European journal of human genetics : EJHG, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 47 citations in OpenAlex.
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- Lateral thinking in syndromic congenital cardiovascular disease.Disease models & mechanisms · 2023Article
- Genetic Alterations of Transcription Factors and Signaling Molecules Involved in the Development of Congenital Heart Defects-A Narrative Review.Children (Basel, Switzerland) · 2023Review
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- Genomic and Non-Genomic Regulatory Mechanisms of the Cardiac Sodium Channel in Cardiac Arrhythmias.International journal of molecular sciences · 2022Review
- Identification of deleterious single nucleotide polymorphism (SNP)s in the humanBiochemistry and biophysics reports · 2021Article
- Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns.Journal of personalized medicine · 2021Review
- TBX5: A Key Regulator of Heart Development.Current topics in developmental biology · 2017Review
- Myocardial transcription factors in diastolic dysfunction: clues for model systems and disease.Heart failure reviews · 2016Review
- Radiographic assessment of congenital malformations of the upper extremity.Pediatric radiology · 2016Review
- A novel de novo TBX5 mutation in a patient with Holt-Oram syndrome leading to a dramatically reduced biological function.Molecular genetics & genomic medicine · 2016Article
- Novel TBX5 duplication in a Japanese family with Holt-Oram syndrome.Pediatric cardiology · 2015Article
- Holt Oram syndrome: a registry-based study in Europe.Orphanet journal of rare diseases · 2014Article
- Insights into the genetic structure of congenital heart disease from human and murine studies on monogenic disorders.Cold Spring Harbor perspectives in medicine · 2014Review
- Holt-Oram: when the key to a broken heart is in the hand.BMJ case reports · 2014Article
- A genetic assay of three patients in the same family with Holt-Oram syndrome; a case report.Reports of biochemistry & molecular biology · 2013Article
- Genetic and genomics in congenital heart disease: a clinical review.Jornal de pediatriaReview
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5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Holt-Oram syndrome (HOS) is a rare autosomal dominant heart-hand syndrome due to mutations in the TBX5 transcription factor. Affected individuals can have structural cardiac defects and/or conduction abnormalities, and exclusively upper limb defects (typically bilateral, asymmetrical radial ray defects). TBX5 mutations reported include nonsense, missense, splicing mutations and exon deletions. Most result in a null allele and haploinsufficiency, but some impair nuclear localisation of TBX5 protein or disrupt its interaction with co-factors and downstream targets. We present a five generation family of nine affected individuals with an atypical HOS phenotype, consisting of ulnar ray defects (ulnar hypoplasia, short fifth fingers with clinodactyly) and very mild radial ray defects (short thumbs, bowing of the radius and dislocation of the radial head). The cardiac defects seen are those more rarely reported in HOS (atrioventricular septal defect, hypoplastic left heart syndrome, mitral valve disease and pulmonary stenosis). Conduction abnormalities include atrial fibrillation, atrial flutter and sick sinus syndrome. TBX5 mutation screening (exons 3-10) identified no mutations. Array comparative genomic hybridisation (CGH) revealed a 48 kb duplication at 12q24.21, encompassing exons 2-9 of the TBX5 gene, with breakpoints within introns 1-2 and 9-10. The duplication segregates with the phenotype in the family, and is likely to be pathogenic. This is the first known report of an intragenic duplication of TBX5 and its clinical effects; an atypical HOS phenotype. Further functional studies are needed to establish the effects of the duplication and pathogenic mechanism. All typical/atypical HOS cases should be screened for TBX5 exon duplications.
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