Back to Search
Start Over
Multiple molecular mechanisms underlying subdiagnostic variants of Marfan syndrome.
- Source :
-
American journal of human genetics [Am J Hum Genet] 1998 Dec; Vol. 63 (6), pp. 1703-11. - Publication Year :
- 1998
-
Abstract
- Mutations in the FBN1 gene, which encodes fibrillin-1, cause Marfan syndrome (MFS) and have been associated with a wide range of milder, overlap phenotypes. The factors that modulate phenotypic severity, both between and within families, remain to be determined. This study examines the relationship between the FBN1 genotype and phenotype in families with extremely mild phenotypes and in those that show striking clinical variation among apparently affected individuals. In one family, clinically similar but etiologically distinct disorders are segregating independently. In another, somatic mosaicism for a mutant FBN1 allele is associated with subdiagnostic manifestations, whereas germ-line transmission of the identical mutation causes severe and rapidly progressive disease. A third family cosegregates mild mitral valve prolapse syndrome with a mutation in FBN1 that can be functionally distinguished from those associated with the classic MFS phenotype. These data have immediate relevance for the diagnostic and prognostic counseling of patients and their family members.
- Subjects :
- Adult
Alleles
Cells, Cultured
Child
Child, Preschool
DNA Mutational Analysis
Female
Fibrillin-1
Fibrillins
Genetic Linkage
Genetic Variation
Genotype
Haplotypes genetics
Heteroduplex Analysis
Humans
Male
Marfan Syndrome diagnosis
Marfan Syndrome pathology
Microfilament Proteins metabolism
Middle Aged
Mitral Valve Prolapse
Mosaicism genetics
Pedigree
Phenotype
Marfan Syndrome genetics
Microfilament Proteins genetics
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9297
- Volume :
- 63
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 9837823
- Full Text :
- https://doi.org/10.1086/302144