skip to main content

Title: Fifteen novel FBN1 mutations causing Marfan syndrome detected by heteroduplex analysis of genomic amplicons

Mutations in the gene encoding fibrillin-1 (FBN1), a component of the extracellular microfibril, cause the Marfan syndrome (MFS). This statement is supported by the observations that the classic Marfan phenotype cosegregates with intragenic and/or flanking marker alleles in all families tested and that a significant number of FBN1 mutations have been identified in affected individuals. We have now devised a method to screen the entire coding sequence and flanking splice junctions of FBN1. On completion for a panel of nine probands with classic MFS, six new mutations were identified that accounted for disease in seven (78%) of nine patients. Nine additional new mutations have been characterized in the early stages of a larger screening project. These 15 mutations were equally distributed throughout the gene and, with one exception, were specific to single families. One-third of mutations created premature termination codons, and 6 of 15 substituted residues with putative significance for calcium finding to epidermal growth factor (EGF)-like domains. Mutations causing severe and rapidly progressive disease that presents in the neonatal period can occur in a larger region of the gene than previously demonstrated, and the nature of the mutation is as important a determinant as its location, in predisposing tomore » this phenotype. 56 refs., 5 figs., 3 tabs.« less
Authors:
; ;  [1]
  1. John Hopkins Univ. School of Medicine, Baltimore, MD (United States) [and others
Publication Date:
OSTI Identifier:
91067
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Human Genetics; Journal Volume: 57; Journal Issue: 1; Other Information: PBD: Jul 1995
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; GENES; GENE MUTATIONS; SIZE; GENETIC MAPPING; PATIENTS; PHENOTYPE; HEREDITARY DISEASES; CONNECTIVE TISSUE; GENETICS; DNA SEQUENCING; POLYMERASE CHAIN REACTION; DOMINANT MUTATIONS; AMINO ACID SEQUENCE; DNA HYBRIDIZATION