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, Omer Günhan, Ahmed A Hidayat, Boris Hügle, Mete Isikoglu, Murat Irkec, Shelagh K Joss, Sonja Klebe, Carolin Kneppo, Idil Kurtulus, Rakesh P Mehta, Kemal Ornek, Reinhard Schneppenheim, Stefan Seregard, Elizabeth Sweeney, Stephanie Turtschi, Gabor Veres, Petra Zeitler, Maike Ziegler, Volker Schuster, 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, Omer Günhan, Ahmed A Hidayat, Boris Hügle, Mete Isikoglu, Murat Irkec, Shelagh K Joss, Sonja Klebe, Carolin Kneppo, Idil Kurtulus, Rakesh P Mehta, Kemal Ornek, Reinhard Schneppenheim, Stefan Seregard, Elizabeth Sweeney, Stephanie Turtschi, Gabor Veres, Petra Zeitler, Maike Ziegler, Volker Schuster
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 PLG proteins as a common molecular pathomechanism in type I PLG deficiency.
Source: PubMed