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Multiple molecular mechanisms underlying subdiagnostic variants of Marfan syndrome.

Authors :
Montgomery RA
Geraghty MT
Bull E
Gelb BD
Johnson M
McIntosh I
Francomano CA
Dietz HC
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.

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