Members of an International Consortium for Linkage Analysis of the Marfan Syndrome (MFS1) have pooled data for joint analysis in an attempt to determine the precise location of the MFS1 gene and the order of 10 DNA markers on 15q.
Mutations in the FBN1 gene encoding the microfibrillar glycoprotein fibrillin cause Marfan syndrome, a relatively common autosomal dominant connective tissue disease.
Characterization of FBN1 mutations in individuals at the most severe end of the Marfan syndrome spectrum should provide greater understanding of the multiple domains and regions of fibrillin.
Since FBN1 is the gene responsible for Marfan syndrome, the information presented here will be useful in identifying new mutations and in understanding the function of fibrillin in the pathogenesis of the disease.
Simple ectopia lentis (EL) was studied in a large family, by clinical examination and analysis of linkage to markers in the region of FBN1, the gene for fibrillin which causes Marfan syndrome on chromosome 15.
We describe here the identification of defined mutations in both alleles of the fibrillin gene (FBN1) in a compound-heterozygote Marfan syndrome (MFS) child who had a very severe form of MFS resulting in death from cardiac failure at the age of 4 mo.
An extra cysteine in one of the non-calcium-binding epidermal growth factor-like motifs of the FBN1 polypeptide is connected to a novel variant of Marfan syndrome.
Interestingly, the neonatal MFS mutations are clustered in one particular region of FBN1, possibly providing new insights into genotype-phenotype comparisons.
Previous studies have mapped the human genes for two fibrillins to chromosome bands 15q21 (FBN1) and 5q23-q31 (FBN2) and have demonstrated that FBN1 mutations are associated with Marfan syndrome, while FBN2 is linked to the gene for congenital contractural arachnodactyly.
More recently, FBN1 has also been shown to harbor mutations related to a spectrum of conditions phenotypically related to MFS and many mutations will have to be accumulated before genotype/phenotype relationships emerge.