Identification of three novel plasminogen (PLG) gene mutations in a series of 23 patients with low PLG activity

Jürgen Klammt, Louise Kobelt, Dilek Aktas, Ismet Durak, Aslan Gokbuget, Quintin Hughes, Murat Irkec, Idil Kurtulus, Elisabetta Lapi, Hadas Mechoulam, Roberto Mendoza-Londono, Joseph S. Palumbo, Hansjörg Steitzer, Khalid F. Tabbara, Zeynep Ozbek, Neri Pucci, Talia Sotomayor, Marian Sturm, Tim Drogies, Maike ZieglerVolker Schuster

Research output: Contribution to journalArticle

Abstract

Inherited severe hypoplasminogenaemia is a multisystemic disorder leading to deficient extravascular fibrinolysis. As a clinical consequence wound healing capacity of mucous membranes is markedly impaired leading to ligneous conjunctivitis and several other manifestations. Here we report the molecular genetic and clinical findings on 23 new cases with severe hypoplasminogenaemia. Homozygous or compound-heterozygous mutations in the plasminogen (PLG) gene were found in 16 of 23 patients (70%), three of which were novel mutations reported here for the first time (C166Y, Y264S, IVS10-7T/G). Compared to 79 previously published cases, clinical manifestations of the current group of patients showed higher percentages of ligneous periodontitis, congenital hydrocephalus, and involvement of the female genital tract. In contrast, involvement of the gastrointestinal or urogenital tract was not observed in any of the cases. Patients originated to a large extent (61%) from Turkey and the Middle East, and showed a comparably frequent occurrence of consanguinity of affected families and a greater female to male ratio than was derived from previous reports in the literature. Individual treatment of ligneous conjunctivitis included topical plasminogen or heparin eye drops, topical or systemic fresh frozen plasma, and surgical removal of ligneous pseudomembranes, mostly with modest or transient efficacy. In conclusion, the present study underscores the broad range of clinical manifestations in PLG-deficient patients with a trend to regional differences. Transmission of genetic and clinical data to the recently established Plasminogen Deficiency Registry should help to determine the prevalence of the disease and to develop more efficient treatment strategies.

Original languageEnglish (US)
Pages (from-to)454-460
Number of pages7
JournalThrombosis and Haemostasis
Volume105
Issue number3
DOIs
StatePublished - Mar 2011
Externally publishedYes

Fingerprint

Plasminogen
Mutation
Genes
Consanguinity
Middle East
Ophthalmic Solutions
Periodontitis
Fibrinolysis
Hydrocephalus
Turkey
Wound Healing
Registries
Heparin
Molecular Biology
Mucous Membrane
Therapeutics
Congenital Plasminogen Deficiency
Type I Plasminogen Deficiency

Keywords

  • Clinical heterogeneity
  • Inherited hypoplasminogenaemia
  • PLG gene mutations

ASJC Scopus subject areas

  • Hematology

Cite this

Klammt, J., Kobelt, L., Aktas, D., Durak, I., Gokbuget, A., Hughes, Q., ... Schuster, V. (2011). Identification of three novel plasminogen (PLG) gene mutations in a series of 23 patients with low PLG activity. Thrombosis and Haemostasis, 105(3), 454-460. https://doi.org/10.1160/TH10-04-0216

Identification of three novel plasminogen (PLG) gene mutations in a series of 23 patients with low PLG activity. / Klammt, Jürgen; Kobelt, Louise; Aktas, Dilek; Durak, Ismet; Gokbuget, Aslan; Hughes, Quintin; Irkec, Murat; Kurtulus, Idil; Lapi, Elisabetta; Mechoulam, Hadas; Mendoza-Londono, Roberto; Palumbo, Joseph S.; Steitzer, Hansjörg; Tabbara, Khalid F.; Ozbek, Zeynep; Pucci, Neri; Sotomayor, Talia; Sturm, Marian; Drogies, Tim; Ziegler, Maike; Schuster, Volker.

In: Thrombosis and Haemostasis, Vol. 105, No. 3, 03.2011, p. 454-460.

Research output: Contribution to journalArticle

Klammt, J, Kobelt, L, Aktas, D, Durak, I, Gokbuget, A, Hughes, Q, Irkec, M, Kurtulus, I, Lapi, E, Mechoulam, H, Mendoza-Londono, R, Palumbo, JS, Steitzer, H, Tabbara, KF, Ozbek, Z, Pucci, N, Sotomayor, T, Sturm, M, Drogies, T, Ziegler, M & Schuster, V 2011, 'Identification of three novel plasminogen (PLG) gene mutations in a series of 23 patients with low PLG activity', Thrombosis and Haemostasis, vol. 105, no. 3, pp. 454-460. https://doi.org/10.1160/TH10-04-0216
Klammt, Jürgen ; Kobelt, Louise ; Aktas, Dilek ; Durak, Ismet ; Gokbuget, Aslan ; Hughes, Quintin ; Irkec, Murat ; Kurtulus, Idil ; Lapi, Elisabetta ; Mechoulam, Hadas ; Mendoza-Londono, Roberto ; Palumbo, Joseph S. ; Steitzer, Hansjörg ; Tabbara, Khalid F. ; Ozbek, Zeynep ; Pucci, Neri ; Sotomayor, Talia ; Sturm, Marian ; Drogies, Tim ; Ziegler, Maike ; Schuster, Volker. / Identification of three novel plasminogen (PLG) gene mutations in a series of 23 patients with low PLG activity. In: Thrombosis and Haemostasis. 2011 ; Vol. 105, No. 3. pp. 454-460.
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