Molecular and clinical spectrum of type I plasminogen deficiency: A series of 50 patients

Katrin Tefs, Maria Gueorguieva, Jürgen Klammt, Carl M. Allen, Dilek Aktas, Fehim Y. Anlar, Sultan D. Aydogdu, Deborah Brown, Ergin Ciftci, Patricia Contarini, Carl Erik Dempfle, Miroslav Dostalek, Susanne Eisert, Aslan Gökbuget, Ömer Günhan, Ahmed A. Hidayat, Boris Hügle, Mete Isikoglu, Murat Irkec, Shelagh K. JossSonja Klebe, Carolin Kneppo, Idil Kurtulus, Rakesh Mehta, Kemal Örnek, Reinhard Schneppenheim, Stefan Seregard, Elizabeth Sweeney, Stephanie Turtschi, Gabor Veres, Petra Zeitler, Maike Ziegler, Volker Schuster

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Severe type I plasminogen (PLG) deficiency has been causally linked to a rare chronic inflammatory disease of the mucous membranes that may be life threatening. Here we report clinical manifestations, PLG plasma levels, and molecular genetic status of the PLG gene of 50 patients. The most common clinical manifestations among these patients were ligneous conjunctivitis (80%) and ligneous gingivitis (34%), followed by less common manifestations such as ligneous vaginitis (8%), and involvement of the respiratory tract (16%), the ears (14%), or the gastrointestinal tract (2%). Four patients showed congenital occlusive hydrocephalus, 2 with Dandy-Walker malformation of cerebellum. Venous thrombosis was not observed. In all patients, plasma PLG levels were markedly reduced. In 38 patients, distinct mutations in the PLG gene were identified. The most common genetic alteration was a K19E mutation found in 34% of patients. Transient in vitro expression of PLG mutants R134K, delK212, R216H, P285T, P285A, T319_N320insN, and R776H in transfected COS-7 cells revealed significantly impaired secretion and increased degradation of PLG. These results demonstrate impaired secretion of mutant PLGproteins as acommonmolecular pathomechanism in type I PLG deficiency.

Original languageEnglish (US)
Pages (from-to)3021-3026
Number of pages6
JournalBlood
Volume108
Issue number9
DOIs
StatePublished - Nov 1 2006
Externally publishedYes

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Plasminogen
Dandy-Walker Syndrome
Vaginitis
Gingivitis
Mutation
Genes
COS Cells
Hydrocephalus
Plasmas
Venous Thrombosis
Respiratory System
Cerebellum
Ear
Gastrointestinal Tract
Type I Plasminogen Deficiency
Molecular Biology
Mucous Membrane
Chronic Disease
Degradation

ASJC Scopus subject areas

  • Hematology

Cite this

Tefs, K., Gueorguieva, M., Klammt, J., Allen, C. M., Aktas, D., Anlar, F. Y., ... Schuster, V. (2006). Molecular and clinical spectrum of type I plasminogen deficiency: A series of 50 patients. Blood, 108(9), 3021-3026. https://doi.org/10.1182/blood-2006-04-017350

Molecular and clinical spectrum of type I plasminogen deficiency : A series of 50 patients. / Tefs, Katrin; Gueorguieva, Maria; Klammt, Jürgen; Allen, Carl M.; Aktas, Dilek; Anlar, Fehim Y.; Aydogdu, Sultan D.; Brown, Deborah; Ciftci, Ergin; Contarini, Patricia; Dempfle, Carl Erik; Dostalek, Miroslav; Eisert, Susanne; Gökbuget, Aslan; Günhan, Ömer; Hidayat, Ahmed A.; Hügle, Boris; Isikoglu, Mete; Irkec, Murat; Joss, Shelagh K.; Klebe, Sonja; Kneppo, Carolin; Kurtulus, Idil; Mehta, Rakesh; Örnek, Kemal; Schneppenheim, Reinhard; Seregard, Stefan; Sweeney, Elizabeth; Turtschi, Stephanie; Veres, Gabor; Zeitler, Petra; Ziegler, Maike; Schuster, Volker.

In: Blood, Vol. 108, No. 9, 01.11.2006, p. 3021-3026.

Research output: Contribution to journalArticle

Tefs, K, Gueorguieva, M, Klammt, J, Allen, CM, Aktas, D, Anlar, FY, Aydogdu, SD, Brown, D, Ciftci, E, Contarini, P, Dempfle, CE, Dostalek, M, Eisert, S, Gökbuget, A, Günhan, Ö, Hidayat, AA, Hügle, B, Isikoglu, M, Irkec, M, Joss, SK, Klebe, S, Kneppo, C, Kurtulus, I, Mehta, R, Örnek, K, Schneppenheim, R, Seregard, S, Sweeney, E, Turtschi, S, Veres, G, Zeitler, P, Ziegler, M & Schuster, V 2006, 'Molecular and clinical spectrum of type I plasminogen deficiency: A series of 50 patients', Blood, vol. 108, no. 9, pp. 3021-3026. https://doi.org/10.1182/blood-2006-04-017350
Tefs K, Gueorguieva M, Klammt J, Allen CM, Aktas D, Anlar FY et al. Molecular and clinical spectrum of type I plasminogen deficiency: A series of 50 patients. Blood. 2006 Nov 1;108(9):3021-3026. https://doi.org/10.1182/blood-2006-04-017350
Tefs, Katrin ; Gueorguieva, Maria ; Klammt, Jürgen ; Allen, Carl M. ; Aktas, Dilek ; Anlar, Fehim Y. ; Aydogdu, Sultan D. ; Brown, Deborah ; Ciftci, Ergin ; Contarini, Patricia ; Dempfle, Carl Erik ; Dostalek, Miroslav ; Eisert, Susanne ; Gökbuget, Aslan ; Günhan, Ömer ; Hidayat, Ahmed A. ; Hügle, Boris ; Isikoglu, Mete ; Irkec, Murat ; Joss, Shelagh K. ; Klebe, Sonja ; Kneppo, Carolin ; Kurtulus, Idil ; Mehta, Rakesh ; Örnek, Kemal ; Schneppenheim, Reinhard ; Seregard, Stefan ; Sweeney, Elizabeth ; Turtschi, Stephanie ; Veres, Gabor ; Zeitler, Petra ; Ziegler, Maike ; Schuster, Volker. / Molecular and clinical spectrum of type I plasminogen deficiency : A series of 50 patients. In: Blood. 2006 ; Vol. 108, No. 9. pp. 3021-3026.
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abstract = "Severe type I plasminogen (PLG) deficiency has been causally linked to a rare chronic inflammatory disease of the mucous membranes that may be life threatening. Here we report clinical manifestations, PLG plasma levels, and molecular genetic status of the PLG gene of 50 patients. The most common clinical manifestations among these patients were ligneous conjunctivitis (80{\%}) and ligneous gingivitis (34{\%}), followed by less common manifestations such as ligneous vaginitis (8{\%}), and involvement of the respiratory tract (16{\%}), the ears (14{\%}), or the gastrointestinal tract (2{\%}). Four patients showed congenital occlusive hydrocephalus, 2 with Dandy-Walker malformation of cerebellum. Venous thrombosis was not observed. In all patients, plasma PLG levels were markedly reduced. In 38 patients, distinct mutations in the PLG gene were identified. The most common genetic alteration was a K19E mutation found in 34{\%} of patients. Transient in vitro expression of PLG mutants R134K, delK212, R216H, P285T, P285A, T319_N320insN, and R776H in transfected COS-7 cells revealed significantly impaired secretion and increased degradation of PLG. These results demonstrate impaired secretion of mutant PLGproteins as acommonmolecular pathomechanism in type I PLG deficiency.",
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AU - Tefs, Katrin

AU - Gueorguieva, Maria

AU - Klammt, Jürgen

AU - Allen, Carl M.

AU - Aktas, Dilek

AU - Anlar, Fehim Y.

AU - Aydogdu, Sultan D.

AU - Brown, Deborah

AU - Ciftci, Ergin

AU - Contarini, Patricia

AU - Dempfle, Carl Erik

AU - Dostalek, Miroslav

AU - Eisert, Susanne

AU - Gökbuget, Aslan

AU - Günhan, Ömer

AU - Hidayat, Ahmed A.

AU - Hügle, Boris

AU - Isikoglu, Mete

AU - Irkec, Murat

AU - Joss, Shelagh K.

AU - Klebe, Sonja

AU - Kneppo, Carolin

AU - Kurtulus, Idil

AU - Mehta, Rakesh

AU - Örnek, Kemal

AU - Schneppenheim, Reinhard

AU - Seregard, Stefan

AU - Sweeney, Elizabeth

AU - Turtschi, Stephanie

AU - Veres, Gabor

AU - Zeitler, Petra

AU - Ziegler, Maike

AU - Schuster, Volker

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