Comprehensive clinical and molecular assessment of 32 probands with congenital contractural arachnodactyly: Report of 14 novel mutations and review of the literature |
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| Authors: | Bert L. Callewaert Bart L. Loeys Anna Ficcadenti Sascha Vermeer Magnus Landgren Hester Y. Kroes Yuval Yaron Michael Pope Nicola Foulds Odile Boute Francisco Galán Helen Kingston Nathalie Van der Aa Iratxe Salcedo Marielle E. Swinkels Carina Wallgren‐Pettersson Orazio Gabrielli Julie De Backer Paul J. Coucke Anne M. De Paepe |
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| Affiliation: | 1. Center for Medical Genetics, Ghent University Hospital, Belgium;2. Paediatric Department, Salesi Children Hospital, Ancona, Italy;3. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands;4. Department of Paediatrics, Skaraborg Hospital, Sk?vde, Sweden;5. Department of Biomedical Genetics, University Medical Center, Utrecht, The Netherlands;6. Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel;7. Institute of Medical Genetics, University Hospital of Wales, Cardiff, UK;8. Department of Pathology, Cambridge University, Cambridge, UK;9. Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK;10. Service de Génétique Clinique, Centre Hospitalier Régional Universitaire de Lille, Lille, France;11. Centro de Genética Humana, Universidad de Alicante, Alicante, Spain;12. Regional Genetic Service, St‐Mary's Hospital, Manchester, UK;13. Center for Medical Genetics, University Hospital of Antwerp, Antwerp, Belgium;14. Center for Medical Genetics, Hospital Comarcal Santiago Apostol, Miranda De Ebro, Burgos, Spain;15. Department of Medical Genetics, University of Helsinki, Helsinki, Finland;16. The Folkh?lsan Institute of Genetics, Helsinki, Finland |
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| Abstract: | Beals‐Hecht syndrome or congenital contractural arachnodactyly (CCA) is a rare, autosomal dominant connective tissue disorder characterized by crumpled ears, arachnodactyly, contractures, and scoliosis. Recent reports also mention aortic root dilatation, a finding previously thought to differentiate the condition from Marfan syndrome (MFS). In many cases, the condition is caused by mutations in the fibrillin 2 gene (FBN2) with 26 mutations reported so far, all located in the middle region of the gene (exons 23–34). We directly sequenced the entire FBN2 gene in 32 probands clinically diagnosed with CCA. In 14 probands, we found 13 new and one previously described FBN2 mutation including a mutation in exon 17, expanding the region in which FBN2 mutations occur in CCA. Review of the literature showed that the phenotype of the FBN2 positive patients was comparable to all previously published FBN2‐positive patients. In our FBN2‐positive patients, cardiovascular involvement included mitral valve prolapse in two adult patients and aortic root enlargement in three patients. Whereas the dilatation regressed in one proband, it remained marked in a child proband (z‐score: 4.09) and his father (z‐score: 2.94), warranting echocardiographic follow‐up. We confirm paradoxical patellar laxity and report keratoconus, shoulder muscle hypoplasia, and pyeloureteral junction stenosis as new features. In addition, we illustrate large intrafamilial variability. Finally, the FBN2‐negative patients in this cohort were clinically indistinguishable from all published FBN2‐positive patients harboring a FBN2 mutation, suggesting locus heterogeneity. Hum Mutat 0, 1–8, 2008. © 2008 Wiley‐Liss, Inc. |
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| Keywords: | congenital contractural arachnodactyly CCA FBN2 fibrillin 2 genotype‐phenotype |
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