Molecular basis of factor xiii deficiency H.Mikkola

V. Yee, L. Muszbek, M. Syrjälä, T. Salmi, R. Seitz, R. Egbring, R. Ljung, P. Petrini, J. Ingerslev, D. Teller, L. Peltonen, A. Palotie

Research output: Contribution to journalArticle

Abstract

Factor XIII deficiency is a rare autosomal recessive bleeding disorder that is characterized by defective crosslinking of fibrin and poor resistance to fibrinolysis. We have characterized seven mutations in FXIII A-subunit gene: Four missense mutations (Met242->Thr. Arg252->Ile, Arg326->Gln and Leu498->Pro) and three nonsense mutations (Arg661->Stop, delT Phe8 and a splicing defect T->C at position +6 in intron C) The expression of FXIII Asubunit was studied in vivo on mRNA and protein level. The structural effects of the mutations were predicted from the three dimensional model of crystallized FXIII A-subunit. (Mikkola et al. Blood 1994, 84:517-525, Mikkola et al. Blood 1996,87:141-151) The missense mutations were further studied by in vitro expression in COS cells. All of them interfere with the enzymatic activity and render the protein susceptible for intracellular degradation. There is considerable phenotypic variation within FXIII deficient patients but little is known about the phenotype-genotype correlation. One of the Finnish patients has an untypically mild phenotype as she has had two succesful pregnancies without FXIII substitutions. She is a compound heterozygote for Arg661->Stop mutation and the splicing mutation (T->C at position +6 of intron C). Analysis of the patients FXIII A-subunit mRNA, antigen and activity in platelets and fibrin cross-linking pattern in plasma suggest partial readthrough of the splicing mutation resulting in a small amount of active enzyme and thus a milder phenotype.

Original languageEnglish
Pages (from-to)78
Number of pages1
JournalFibrinolysis
Volume10
Issue numberSUPPL. 3
Publication statusPublished - 1996

Fingerprint

Mutation
Missense Mutation
Fibrin
Introns
Factor XIII Deficiency
Phenotype
Messenger RNA
Nonsense Codon
COS Cells
Genetic Association Studies
Fibrinolysis
Heterozygote
Proteins
Blood Platelets
Complement Factor H Deficiency
Hemorrhage
Antigens
Pregnancy
Enzymes
Genes

ASJC Scopus subject areas

  • Hematology

Cite this

Yee, V., Muszbek, L., Syrjälä, M., Salmi, T., Seitz, R., Egbring, R., ... Palotie, A. (1996). Molecular basis of factor xiii deficiency H.Mikkola. Fibrinolysis, 10(SUPPL. 3), 78.

Molecular basis of factor xiii deficiency H.Mikkola. / Yee, V.; Muszbek, L.; Syrjälä, M.; Salmi, T.; Seitz, R.; Egbring, R.; Ljung, R.; Petrini, P.; Ingerslev, J.; Teller, D.; Peltonen, L.; Palotie, A.

In: Fibrinolysis, Vol. 10, No. SUPPL. 3, 1996, p. 78.

Research output: Contribution to journalArticle

Yee, V, Muszbek, L, Syrjälä, M, Salmi, T, Seitz, R, Egbring, R, Ljung, R, Petrini, P, Ingerslev, J, Teller, D, Peltonen, L & Palotie, A 1996, 'Molecular basis of factor xiii deficiency H.Mikkola', Fibrinolysis, vol. 10, no. SUPPL. 3, pp. 78.
Yee V, Muszbek L, Syrjälä M, Salmi T, Seitz R, Egbring R et al. Molecular basis of factor xiii deficiency H.Mikkola. Fibrinolysis. 1996;10(SUPPL. 3):78.
Yee, V. ; Muszbek, L. ; Syrjälä, M. ; Salmi, T. ; Seitz, R. ; Egbring, R. ; Ljung, R. ; Petrini, P. ; Ingerslev, J. ; Teller, D. ; Peltonen, L. ; Palotie, A. / Molecular basis of factor xiii deficiency H.Mikkola. In: Fibrinolysis. 1996 ; Vol. 10, No. SUPPL. 3. pp. 78.
@article{97914321cc934c33bbe0eb8781d8295d,
title = "Molecular basis of factor xiii deficiency H.Mikkola",
abstract = "Factor XIII deficiency is a rare autosomal recessive bleeding disorder that is characterized by defective crosslinking of fibrin and poor resistance to fibrinolysis. We have characterized seven mutations in FXIII A-subunit gene: Four missense mutations (Met242->Thr. Arg252->Ile, Arg326->Gln and Leu498->Pro) and three nonsense mutations (Arg661->Stop, delT Phe8 and a splicing defect T->C at position +6 in intron C) The expression of FXIII Asubunit was studied in vivo on mRNA and protein level. The structural effects of the mutations were predicted from the three dimensional model of crystallized FXIII A-subunit. (Mikkola et al. Blood 1994, 84:517-525, Mikkola et al. Blood 1996,87:141-151) The missense mutations were further studied by in vitro expression in COS cells. All of them interfere with the enzymatic activity and render the protein susceptible for intracellular degradation. There is considerable phenotypic variation within FXIII deficient patients but little is known about the phenotype-genotype correlation. One of the Finnish patients has an untypically mild phenotype as she has had two succesful pregnancies without FXIII substitutions. She is a compound heterozygote for Arg661->Stop mutation and the splicing mutation (T->C at position +6 of intron C). Analysis of the patients FXIII A-subunit mRNA, antigen and activity in platelets and fibrin cross-linking pattern in plasma suggest partial readthrough of the splicing mutation resulting in a small amount of active enzyme and thus a milder phenotype.",
author = "V. Yee and L. Muszbek and M. Syrj{\"a}l{\"a} and T. Salmi and R. Seitz and R. Egbring and R. Ljung and P. Petrini and J. Ingerslev and D. Teller and L. Peltonen and A. Palotie",
year = "1996",
language = "English",
volume = "10",
pages = "78",
journal = "Fibrinolysis and Proteolysis",
issn = "0268-9499",
publisher = "Churchill Livingstone",
number = "SUPPL. 3",

}

TY - JOUR

T1 - Molecular basis of factor xiii deficiency H.Mikkola

AU - Yee, V.

AU - Muszbek, L.

AU - Syrjälä, M.

AU - Salmi, T.

AU - Seitz, R.

AU - Egbring, R.

AU - Ljung, R.

AU - Petrini, P.

AU - Ingerslev, J.

AU - Teller, D.

AU - Peltonen, L.

AU - Palotie, A.

PY - 1996

Y1 - 1996

N2 - Factor XIII deficiency is a rare autosomal recessive bleeding disorder that is characterized by defective crosslinking of fibrin and poor resistance to fibrinolysis. We have characterized seven mutations in FXIII A-subunit gene: Four missense mutations (Met242->Thr. Arg252->Ile, Arg326->Gln and Leu498->Pro) and three nonsense mutations (Arg661->Stop, delT Phe8 and a splicing defect T->C at position +6 in intron C) The expression of FXIII Asubunit was studied in vivo on mRNA and protein level. The structural effects of the mutations were predicted from the three dimensional model of crystallized FXIII A-subunit. (Mikkola et al. Blood 1994, 84:517-525, Mikkola et al. Blood 1996,87:141-151) The missense mutations were further studied by in vitro expression in COS cells. All of them interfere with the enzymatic activity and render the protein susceptible for intracellular degradation. There is considerable phenotypic variation within FXIII deficient patients but little is known about the phenotype-genotype correlation. One of the Finnish patients has an untypically mild phenotype as she has had two succesful pregnancies without FXIII substitutions. She is a compound heterozygote for Arg661->Stop mutation and the splicing mutation (T->C at position +6 of intron C). Analysis of the patients FXIII A-subunit mRNA, antigen and activity in platelets and fibrin cross-linking pattern in plasma suggest partial readthrough of the splicing mutation resulting in a small amount of active enzyme and thus a milder phenotype.

AB - Factor XIII deficiency is a rare autosomal recessive bleeding disorder that is characterized by defective crosslinking of fibrin and poor resistance to fibrinolysis. We have characterized seven mutations in FXIII A-subunit gene: Four missense mutations (Met242->Thr. Arg252->Ile, Arg326->Gln and Leu498->Pro) and three nonsense mutations (Arg661->Stop, delT Phe8 and a splicing defect T->C at position +6 in intron C) The expression of FXIII Asubunit was studied in vivo on mRNA and protein level. The structural effects of the mutations were predicted from the three dimensional model of crystallized FXIII A-subunit. (Mikkola et al. Blood 1994, 84:517-525, Mikkola et al. Blood 1996,87:141-151) The missense mutations were further studied by in vitro expression in COS cells. All of them interfere with the enzymatic activity and render the protein susceptible for intracellular degradation. There is considerable phenotypic variation within FXIII deficient patients but little is known about the phenotype-genotype correlation. One of the Finnish patients has an untypically mild phenotype as she has had two succesful pregnancies without FXIII substitutions. She is a compound heterozygote for Arg661->Stop mutation and the splicing mutation (T->C at position +6 of intron C). Analysis of the patients FXIII A-subunit mRNA, antigen and activity in platelets and fibrin cross-linking pattern in plasma suggest partial readthrough of the splicing mutation resulting in a small amount of active enzyme and thus a milder phenotype.

UR - http://www.scopus.com/inward/record.url?scp=33846675123&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846675123&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33846675123

VL - 10

SP - 78

JO - Fibrinolysis and Proteolysis

JF - Fibrinolysis and Proteolysis

SN - 0268-9499

IS - SUPPL. 3

ER -