Recurrent mis-splicing of fibrillin exon 32 in two patients with neonatal marfan syndrome

M. Wang, C. E. Price, J. Nan, J. Cisler, K. Imaizumi, M. Noelle van Thienen, A. DePaepe, Maurice Godfrey

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The Marfan syndrome (MFS) is an autosomal domainant heritable disorder of connective tissue. Variable and plelotropic clinical features are observed in the skeletal, ocular, and cardiovascular systems. The most severe end of the phenotypic spectrum of this disorder comprises a group of patients usually diagnosed at birth, who have a life expectancy of little more than a year, To distinguish this group of patients from those with classical MFS, we refer to them as neonatal Marfan syndrome (nMFS). These infants usually die of congestive heart failure rather than aortic aneurysmal disease, the most frequent cause of morbidity and mortality in classical MFS. Defects in fibrillin, an elastin-associated microfibrillar glycoprotein, are now known to cause both the classical and neonatal forms of MFS. Here we report the recurrent mis-splicing of fibrillin (FBN1) exon 32, a precursor EGF-like calcium binding domain, in two unrelated infants with nMFS. The mis-splicing, in one patient, was dur to an A→T transversion at the -2 position of the consensus acceptor splice site; while that in the second patient was caused by a G→A transition at the + position of the donor splice site. Characterization ofFBN1 mutations in individuals at the most severe end of the Marfan syndrome spectrum should provide greater understanding of the multiple domains and regions of fibrillin. / 1995 Oxford University Press.

Original languageEnglish (US)
Pages (from-to)607-613
Number of pages7
JournalHuman Molecular Genetics
Volume4
Issue number4
DOIs
StatePublished - Apr 1 1995

Fingerprint

Marfan Syndrome
Exons
RNA Splice Sites
Aortic Diseases
Elastin
Cardiovascular System
Life Expectancy
Fibrillins
Epidermal Growth Factor
Connective Tissue
Heart Failure
Parturition
Calcium
Morbidity
Mutation
Mortality

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Recurrent mis-splicing of fibrillin exon 32 in two patients with neonatal marfan syndrome. / Wang, M.; Price, C. E.; Nan, J.; Cisler, J.; Imaizumi, K.; Noelle van Thienen, M.; DePaepe, A.; Godfrey, Maurice.

In: Human Molecular Genetics, Vol. 4, No. 4, 01.04.1995, p. 607-613.

Research output: Contribution to journalArticle

Wang, M, Price, CE, Nan, J, Cisler, J, Imaizumi, K, Noelle van Thienen, M, DePaepe, A & Godfrey, M 1995, 'Recurrent mis-splicing of fibrillin exon 32 in two patients with neonatal marfan syndrome', Human Molecular Genetics, vol. 4, no. 4, pp. 607-613. https://doi.org/10.1093/hmg/4.4.607
Wang M, Price CE, Nan J, Cisler J, Imaizumi K, Noelle van Thienen M et al. Recurrent mis-splicing of fibrillin exon 32 in two patients with neonatal marfan syndrome. Human Molecular Genetics. 1995 Apr 1;4(4):607-613. https://doi.org/10.1093/hmg/4.4.607
Wang, M. ; Price, C. E. ; Nan, J. ; Cisler, J. ; Imaizumi, K. ; Noelle van Thienen, M. ; DePaepe, A. ; Godfrey, Maurice. / Recurrent mis-splicing of fibrillin exon 32 in two patients with neonatal marfan syndrome. In: Human Molecular Genetics. 1995 ; Vol. 4, No. 4. pp. 607-613.
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