Dataset Information

The clinical spectrum of complete FBN1 allele deletions.

ABSTRACT: The most common mutations found in FBN1 are missense mutations (56%), mainly substituting or creating a cysteine in a cbEGF domain. Other mutations are frameshift, splice and nonsense mutations. There are only a few reports of patients with marfanoid features and a molecularly proven complete deletion of a FBN1 allele. We describe the clinical features of 10 patients with a complete FBN1 gene deletion. Seven patients fulfilled the Ghent criteria for Marfan syndrome (MFS). The other three patients were examined at a young age and did not (yet) present the full clinical picture of MFS yet. Ectopia lentis was present in at least two patients. Aortic root dilatation was present in 6 of the 10 patients. In three patients, the aortic root diameter was on the 95th percentile and in one patient, the diameter of the aortic root was normal, the cross-section, however, had a cloverleaf appearance. Two patients underwent aortic root surgery at a relatively young age (27 and 34 years). Mitral valve prolapse was present in 4 of the 10 patients, and billowing of the mitral valve in 1. All patients had facial and skeletal features of MFS. Two patients with a large deletion extending beyond the FBN1 gene had an extended phenotype. We conclude that complete loss of one FBN1 allele does not predict a mild phenotype, and these findings support the hypothesis that true haploinsufficiency can lead to the classical phenotype of Marfan syndrome.

SUBMITTER: Hilhorst-Hofstee Y

PROVIDER: S-EPMC3061999 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The clinical spectrum of complete FBN1 allele deletions.

Hilhorst-Hofstee Yvonne Y Hamel Ben C J BC Verheij Joke B G M JB Rijlaarsdam Marry E B ME Mancini Grazia M S GM Cobben Jan M JM Giroth Cindy C Ruivenkamp Claudia A L CA Hansson Kerstin B M KB Timmermans Janneke J Moll Henriette A HA Breuning Martijn H MH Pals Gerard G

European journal of human genetics : EJHG 20101110 3

The most common mutations found in FBN1 are missense mutations (56%), mainly substituting or creating a cysteine in a cbEGF domain. Other mutations are frameshift, splice and nonsense mutations. There are only a few reports of patients with marfanoid features and a molecularly proven complete deletion of a FBN1 allele. We describe the clinical features of 10 patients with a complete FBN1 gene deletion. Seven patients fulfilled the Ghent criteria for Marfan syndrome (MFS). The other three patient ...[more]

PMID: 21063442

Similar Datasets

Project description:Connective tissue diseases characterized by aortic aneurysm, such as Marfan syndrome, Loeys-Dietz syndrome and Ehlers Danlos syndrome type IV are heterogeneous and despite overlapping phenotypes, the natural history, clinical manifestations and interventional course for each diagnosis can be quite unique. The majority of mutations involved in the etiology of these disorders are missense and nonsense mutations. However, large deletions and duplications undetected by sequencing may be implicated in their pathogenesis, and may explain the apparent lack of genotype-phenotype correlation in a subset of patients. The objective of this study was to search for large pathogenic deletions and/or duplications in the FBN1, TGF?R1, and TGF?R2 genes using multiplex-ligation dependent probe amplification (MLPA) in patients with aortopathy, in whom no mutations in the FBN1, TGF?R1, and TGF?R2 genes were identified by sequencing.The study included 14 patients from 11 unrelated families with aortic aneurysm. Of those, six patients (including 3 first-degree relatives), fulfilled the revised Ghent criteria for Marfan syndrome, and eight had predominantly aortic aneurysm/dilatation with variable skeletal and craniofacial involvement. MLPA for FBN1, TGF?R1, and TGF?R2 was carried out in all patients. A 385 K chromosome 15 specific array was used in two patients with a deletion of the entire FBN1 in order to define its size and boundaries.We identified two novel large deletions in the FBN1 gene in four patients of two unrelated families who met clinical diagnostic criteria for Marfan syndrome. One patient was found to have a FBN1 deletion encompassing exons 1-5. The other three patients had a 542 Kb deletion spanning the whole FBN1 gene and five additional genes (SLC24A5, MYEF2, CTXN2, SLC12A1, DUT) in the chromosome 15.Our findings expand the number of large FBN1 deletions, and emphasize the importance of screening for large genomic deletions in connective tissue disorders featuring aortopathies, especially for those with classic Marfan phenotype.

Dataset Information

The clinical spectrum of complete FBN1 allele deletions.

Publications

The clinical spectrum of complete FBN1 allele deletions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets