Two mutations in Marfan syndrome resulting in truncated fibrillin polypeptides

K. Kainulainen, Lynn Sakai, A. Child, F. M. Pope, L. Puhakka, L. Ryhanen, A. Palotie, I. Kaitila, L. Peltonen

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Biochemical and molecular genetic studies have recently suggested that mutations in the gene coding for fibrillin on chromosome 15 result in Marfan syndrome. To our knowledge, only one mutation in the fibrillin gene has been published. Here we report the results of screening 20 unrelated MFS patients for mutations in fibrillin cDNA by the single-strand conformation polymorphism technique. We found two mutations, both of which appear in the heterozygote form and code for a shortened fibrillin polypeptide. The first mutation is a large in-frame deletion of 366 bases of the fibrillin mRNA, shown to result in a truncated but secreted polypeptide found in the fibroblast culture of the patient. The second mutation is a G-to-A transition resulting in the substitution of a stop codon for a tryptophan codon and thus predicting the premature termination of the polypeptide chain. We screened 60 other, unrelated MFS patients for these mutations as well as for the previously reported mutation (arginine-239 to proline) and found none of the three mutations in any of these patients. These data suggest that most MFS families carry their own distinct mutation.

Original languageEnglish (US)
Pages (from-to)5917-5921
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number13
DOIs
StatePublished - Jul 20 1992
Externally publishedYes

Fingerprint

Marfan Syndrome
Peptides
Mutation
Molecular Biology
Fibrillins
Chromosomes, Human, Pair 15
Terminator Codon
Heterozygote
Proline
Codon
Tryptophan
Genes
Arginine
Complementary DNA
Fibroblasts

ASJC Scopus subject areas

  • General

Cite this

Two mutations in Marfan syndrome resulting in truncated fibrillin polypeptides. / Kainulainen, K.; Sakai, Lynn; Child, A.; Pope, F. M.; Puhakka, L.; Ryhanen, L.; Palotie, A.; Kaitila, I.; Peltonen, L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 13, 20.07.1992, p. 5917-5921.

Research output: Contribution to journalArticle

Kainulainen, K, Sakai, L, Child, A, Pope, FM, Puhakka, L, Ryhanen, L, Palotie, A, Kaitila, I & Peltonen, L 1992, 'Two mutations in Marfan syndrome resulting in truncated fibrillin polypeptides', Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 13, pp. 5917-5921. https://doi.org/10.1073/pnas.89.13.5917
Kainulainen, K. ; Sakai, Lynn ; Child, A. ; Pope, F. M. ; Puhakka, L. ; Ryhanen, L. ; Palotie, A. ; Kaitila, I. ; Peltonen, L. / Two mutations in Marfan syndrome resulting in truncated fibrillin polypeptides. In: Proceedings of the National Academy of Sciences of the United States of America. 1992 ; Vol. 89, No. 13. pp. 5917-5921.
@article{2deb009cd4da4b20a3adc66b740ee24d,
title = "Two mutations in Marfan syndrome resulting in truncated fibrillin polypeptides",
abstract = "Biochemical and molecular genetic studies have recently suggested that mutations in the gene coding for fibrillin on chromosome 15 result in Marfan syndrome. To our knowledge, only one mutation in the fibrillin gene has been published. Here we report the results of screening 20 unrelated MFS patients for mutations in fibrillin cDNA by the single-strand conformation polymorphism technique. We found two mutations, both of which appear in the heterozygote form and code for a shortened fibrillin polypeptide. The first mutation is a large in-frame deletion of 366 bases of the fibrillin mRNA, shown to result in a truncated but secreted polypeptide found in the fibroblast culture of the patient. The second mutation is a G-to-A transition resulting in the substitution of a stop codon for a tryptophan codon and thus predicting the premature termination of the polypeptide chain. We screened 60 other, unrelated MFS patients for these mutations as well as for the previously reported mutation (arginine-239 to proline) and found none of the three mutations in any of these patients. These data suggest that most MFS families carry their own distinct mutation.",
author = "K. Kainulainen and Lynn Sakai and A. Child and Pope, {F. M.} and L. Puhakka and L. Ryhanen and A. Palotie and I. Kaitila and L. Peltonen",
year = "1992",
month = "7",
day = "20",
doi = "10.1073/pnas.89.13.5917",
language = "English (US)",
volume = "89",
pages = "5917--5921",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "13",

}

TY - JOUR

T1 - Two mutations in Marfan syndrome resulting in truncated fibrillin polypeptides

AU - Kainulainen, K.

AU - Sakai, Lynn

AU - Child, A.

AU - Pope, F. M.

AU - Puhakka, L.

AU - Ryhanen, L.

AU - Palotie, A.

AU - Kaitila, I.

AU - Peltonen, L.

PY - 1992/7/20

Y1 - 1992/7/20

N2 - Biochemical and molecular genetic studies have recently suggested that mutations in the gene coding for fibrillin on chromosome 15 result in Marfan syndrome. To our knowledge, only one mutation in the fibrillin gene has been published. Here we report the results of screening 20 unrelated MFS patients for mutations in fibrillin cDNA by the single-strand conformation polymorphism technique. We found two mutations, both of which appear in the heterozygote form and code for a shortened fibrillin polypeptide. The first mutation is a large in-frame deletion of 366 bases of the fibrillin mRNA, shown to result in a truncated but secreted polypeptide found in the fibroblast culture of the patient. The second mutation is a G-to-A transition resulting in the substitution of a stop codon for a tryptophan codon and thus predicting the premature termination of the polypeptide chain. We screened 60 other, unrelated MFS patients for these mutations as well as for the previously reported mutation (arginine-239 to proline) and found none of the three mutations in any of these patients. These data suggest that most MFS families carry their own distinct mutation.

AB - Biochemical and molecular genetic studies have recently suggested that mutations in the gene coding for fibrillin on chromosome 15 result in Marfan syndrome. To our knowledge, only one mutation in the fibrillin gene has been published. Here we report the results of screening 20 unrelated MFS patients for mutations in fibrillin cDNA by the single-strand conformation polymorphism technique. We found two mutations, both of which appear in the heterozygote form and code for a shortened fibrillin polypeptide. The first mutation is a large in-frame deletion of 366 bases of the fibrillin mRNA, shown to result in a truncated but secreted polypeptide found in the fibroblast culture of the patient. The second mutation is a G-to-A transition resulting in the substitution of a stop codon for a tryptophan codon and thus predicting the premature termination of the polypeptide chain. We screened 60 other, unrelated MFS patients for these mutations as well as for the previously reported mutation (arginine-239 to proline) and found none of the three mutations in any of these patients. These data suggest that most MFS families carry their own distinct mutation.

UR - http://www.scopus.com/inward/record.url?scp=0026667139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026667139&partnerID=8YFLogxK

U2 - 10.1073/pnas.89.13.5917

DO - 10.1073/pnas.89.13.5917

M3 - Article

C2 - 1631074

AN - SCOPUS:0026667139

VL - 89

SP - 5917

EP - 5921

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 13

ER -