Comprehensive clinical and molecular assessment of 32 probands with congenital contractural arachnodactyly: report of 14 novel mutations and review of the literature.
Fulltext:
81654.pdf
Embargo:
until further notice
Size:
205.1Kb
Format:
PDF
Description:
Publisher’s version
Publication year
2009Source
Human Mutation, 30, 3, (2009), pp. 334-41ISSN
Publication type
Article / Letter to editor
Display more detailsDisplay less details
Organization
Human Genetics
Former Organization
Radboud University Nijmegen Medical Centre
Journal title
Human Mutation
Volume
vol. 30
Issue
iss. 3
Page start
p. 334
Page end
p. 41
Subject
IGMD 3: Genomic disorders and inherited multi-system disordersAbstract
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.
This item appears in the following Collection(s)
- Academic publications [238441]
- Electronic publications [122537]
- Faculty of Medical Sciences [90373]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.