A Novel Mutation of the Fibrillin Gene Causing Ectopia Lentis

Lönnqvist, Lasse; Child, A. H.; Kainulainen, Katariina; Davidson, Rebecca M.; Puhakka, Lea; Peltonen, Leena

doi:10.1006/geno.1994.1110

Cited by 85 publications

(54 citation statements)

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“…A series of fibrillinopathies characterized by various combinations of ocular and skeletal abnormalities without aortic dilatation has been reported, including isolated ectopia lentis [Lönnqvist et al, 1994] and isolated skeletal involvement [Milewicz et al, 1995]. Results published to date suggest that a significant subset of mutations located in exons 59-65 (the last seven exons of FBN1) are associated with mild fibrillinopathies.…”

Section: Mild Marfan-like Disorders Without Aortic Dissectionmentioning

confidence: 95%

Mutations of FBN1 and genotype-phenotype correlations in Marfan syndrome and related fibrillinopathies

et al. 2002

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The Marfan syndrome (MFS) is a pleiotropic, autosomal dominant disorder of connective tissue with highly variable clinical manifestations including aortic dilatation and dissection, ectopia lentis, and a series of skeletal anomalies. Mutations in the gene for fibrillin-1 (FBN1) cause MFS, and at least 337 mainly unique mutations have been published to date. FBN1 mutations have been found not only in MFS but also in a range of connective tissue disorders collectively termed fibrillinopathies ranging from mild phenotypes, such as isolated ectopia lentis, to severe disorders including neonatal MFS, which generally leads to death within the first two years of life. The present article intends to provide an overview of mutations found in MFS and related disorders and to discuss potential genotype-phenotype correlations in MFS.

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Section: Mild Marfan-like Disorders Without Aortic Dissectionmentioning

confidence: 95%

Mutations of FBN1 and genotype-phenotype correlations in Marfan syndrome and related fibrillinopathies

et al. 2002

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“…On the other hand, if one uses a strict clinical definition of neonatal MFS, mutations associated with neonatal MFS have been found to cluster in exons 24-27 and 31-32 [Booms et al, 1999]. Additionally, individual mutations have been shown to cosegregate in families with various atypical phenotypes, including autosomal dominant ectopia lentis [Lönnqvist et al, 1994], isolated skeletal manifestations [Milewicz et al, 1995], and familial ascending aortic aneurysm and dissection (fAAA) [Francke et al, 1995]. In the majority of cases, exon-skipping mutations are associated with severe phenotypes [Liu et al, 1996].…”

Section: Introductionmentioning

confidence: 96%

“…On the other hand, mutations affecting an analogous residue within two different modules may also be associated with differing phenotypes. For instance, the mutation E2447K affects the fifth residue of cbEGF module #38 and is associated with autosomal dominant ectopia lentis [Lönnqvist et al, 1994]; the mutation E1073K causes an analogous change of the fifth residue of cbEGF module #12 and is associated with neonatal MFS [Nijbroek et al, 1995]. Therefore, it is apparent that neither the location of the affected structural module in the protein nor the position of the altered residue is in itself sufficient to predict potential genotype-phenotype correlations.…”

Section: Introductionmentioning

confidence: 97%

Clustering of mutations associated with mild Marfan-like phenotypes in the 3? region ofFBN1 suggests a potential genotype-phenotype correlation

et al. 2000

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Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, a dominantly inherited disorder of connective tissue that primarily involves the cardiovascular, ocular, and skeletal systems. There is a remarkable degree of variability both within and between families with Marfan syndrome, and FBN1 mutations have also been found in a range of other related connective tissue disorders collectively termed type-1 fibrillinopathies. FBN1 mutations have been found in almost all of the 65 exons of the FBN1 gene and for the most part have been unique to one affected patient or family. Aside from the "hot spots" for the neonatal Marfan syndrome in exons 24-27 and 31-32, genotype-phenotype correlations have been slow to emerge. Here we present the results of temperature-gradient gel electrophoresis analysis of FBN1 exons 59-65. Six mutations were identified, only one of which had been previously reported. Two of the six mutations were found in patients with mild phenotypes. Taken together with other published reports, our results suggest that a sizable subset (ca. 40%) of mutations in this region is associated with mild phenotypes characterized by the lack of significant aortic pathology, compared with about 7% in the rest of the gene. In two cases, mutations affecting analogous positions within one of the 43 cbEGF modules of FBN1 are associated with mild phenotypes when found in one of the 6 C-terminal modules (encoded by exons 59-63), but are associated with classic or severe phenotypes when found in cbEGF modules elsewhere in the gene.

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“…Indeed, some teams propose to install medical therapy only when regular echocardiograms do demonstrate some definite progressive involvement, arguing that some families with ocular and skeletal manifestations only do not demonstrate cardiac involvement. 33 …”

Section: Negative Clinical Predictive Value (Probability Not To Develmentioning

confidence: 99%

Clinical utility gene card for: Marfan syndrome type 1 and related phenotypes [FBN1]

et al. 2010

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A Novel Mutation of the Fibrillin Gene Causing Ectopia Lentis

Cited by 85 publications

References 0 publications

Mutations of FBN1 and genotype-phenotype correlations in Marfan syndrome and related fibrillinopathies

Mutations of FBN1 and genotype-phenotype correlations in Marfan syndrome and related fibrillinopathies

Clustering of mutations associated with mild Marfan-like phenotypes in the 3? region ofFBN1 suggests a potential genotype-phenotype correlation

Clinical utility gene card for: Marfan syndrome type 1 and related phenotypes [FBN1]

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