skip to main content

Title: Delineation of the Marfan phenotype associated with mutations in exons 23-32 of the FBN1 gene

Marfan syndrome is a dominantly inherited connective tissue disorder with a wide range of phenotypic severity. The condition is the result of mutations in FBN1, a large gene composed of 65 exons encoding the fibrillin-1 protein. While mutations causing classic manifestations of Marfan syndrome have been identified throughout the FBN1 gene, the six previously characterized mutations resulting in the severe, perinatal lethal form of Marfan syndrome have clustered in exons 24-32 of the gene. We screened 8 patients with either neonatal Marfan syndrome or severe cardiovascular complications of Marfan syndrome for mutations in this region of the gene. Using intron-based exon-specific primers, we amplified exons 23-32 from genomic DNAs, screened these fragments by single-stranded conformational polymorphism analysis, and sequenced indicated exons. This analysis documented mutations in exons 25-27 of the FBN1 mutations in 6 of these patients. These results, taken together with previously published FBN1 mutations in this region, further define the phenotype associated with mutations in exons 24-32 of the FBN1 gene, information important for the development of possible diagnostic tests and genetic counseling. 49 refs., 4 figs., 2 tabs.
Authors:
; ;  [1]
  1. Univ. of Texas-Houston Medical School, Houston, TX (United States) [and others
Publication Date:
OSTI Identifier:
426139
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Medical Genetics; Journal Volume: 62; Journal Issue: 3; Other Information: PBD: 29 Mar 1996
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; PATIENTS; HEREDITARY DISEASES; CONGENITAL DISEASES; PHENOTYPE; CARDIOVASCULAR DISEASES; GENES; GENETIC MAPPING; GENE MUTATIONS; STRUCTURE-ACTIVITY RELATIONSHIPS; GENE AMPLIFICATION; DETECTION; CONNECTIVE TISSUE; PROTEINS; EXONS; DOMINANT MUTATIONS; INTRONS; DNA SEQUENCING