Delineation of the Marfan Phenotype Associated with Mutations in Exons 23-32 of the FBN1 Gene

Elizabeth A. Putnam, Mimi Cho, Arthur B. Zinn, Jeffrey Towbin, Peter H. Byers, Dianna M. Milewicz

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

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 gene 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.

Original languageEnglish (US)
Pages (from-to)233-242
Number of pages10
JournalAmerican Journal of Medical Genetics - Seminars in Medical Genetics
Volume62
Issue number3
DOIs
StatePublished - Mar 29 1996
Externally publishedYes

Fingerprint

Marfan Syndrome
Exons
Phenotype
Mutation
Genes
Single-Stranded Conformational Polymorphism
Genetic Counseling
Routine Diagnostic Tests
Connective Tissue
Introns
DNA
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Delineation of the Marfan Phenotype Associated with Mutations in Exons 23-32 of the FBN1 Gene. / Putnam, Elizabeth A.; Cho, Mimi; Zinn, Arthur B.; Towbin, Jeffrey; Byers, Peter H.; Milewicz, Dianna M.

In: American Journal of Medical Genetics - Seminars in Medical Genetics, Vol. 62, No. 3, 29.03.1996, p. 233-242.

Research output: Contribution to journalArticle

Putnam, Elizabeth A. ; Cho, Mimi ; Zinn, Arthur B. ; Towbin, Jeffrey ; Byers, Peter H. ; Milewicz, Dianna M. / Delineation of the Marfan Phenotype Associated with Mutations in Exons 23-32 of the FBN1 Gene. In: American Journal of Medical Genetics - Seminars in Medical Genetics. 1996 ; Vol. 62, No. 3. pp. 233-242.
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