Linked Life Data

10694921

Source:http://linkedlifedata.com/resource/pubmed/id/10694921

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-1-18
pubmed:abstractText
Marfan Syndrome (MfS) is an autosomal dominant inherited connective tissue disorder with variable phenotypic expression of cardiovascular, skeletal and ocular manifestations. Cardiovascular complications, such as aortic aneurysm and dissection drastically reduce life expectancy of individuals with MfS, whereas preventive surgery substantially improves the prognosis of these patients. A number of mutations in the fibrillin 1 (FBN1) gene associated with MfS have been identified to date, demonstrating considerable molecular heterogeneity. One region, however, located around exon 24, exhibits a striking clustering of mutations, which are associated with a severe, socalled neonatal form of MfS. Here we report the first mutation (G2950A) in exon 24 of the neonatal region of the FBN1 gene, associated with a classic MfS phenotype. The mutation leads to the subsitution of valin by isoleucin (V984I), both uncharged amino acids, which only differ in a single methyl group. This defect was identified in a proband with cardiovascular manifestations of MfS by SSCP analysis of PCR-amplified genomic DNA, direct PCR sequencing and RFLP analysis. The substitution was neither detected in the unaffected 4-year old daughter of the proband, nor in 3 of his healthy family members nor in 108 allels from control individuals, suggesting that this mutation is causative for MfS in the patient. Since no other family member of the proband is affected by MfS, the defect described is sporadic. In summary, we identified a novel defect in exon 24 of the neonatal region of the FBN1 gene in a patient with a classic phenotype of MfS, suggesting that conservative substitutions in this region may lead to a less severe phenotype of the disease. This finding further demonstrates the remarkable phenotypic heterogeneity associated with FBN1 mutations and stresses the significance of modifying genes and individual alterations in protein function for the pheontypic expression of the disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1059-7794
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
137
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
A novel mutation in the neonatal region of the fibrillin (FBN)1 gene associated with a classical phenotype of Marfan syndrome (MfS). Mutations in brief no. 163. Online.
pubmed:affiliation
Department of Cardiovascular Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, D-81366 München, Germany.
pubmed:publicationType
Journal Article