title: Molecular and clinical spectrum of type I plasminogen deficiency: A series of 50 patients.
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.
authors.affiliation: Hospital for Children and Adolescents, University of Leipzig, Oststrasse 21-25, D-04317 Leipzig, Germany. katrin.tefs@medizin.uni-leipzig.de
authors.forename: Katrin
authors.initials: K
authors.lastname: Tefs
authors.forename: Maria
authors.initials: M
authors.lastname: Gueorguieva
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klammt
authors.forename: Carl M
authors.initials: CM
authors.lastname: Allen
authors.forename: Dilek
authors.initials: D
authors.lastname: Aktas
authors.forename: Fehim Y
authors.initials: FY
authors.lastname: Anlar
authors.forename: Sultan D
authors.initials: SD
authors.lastname: Aydogdu
authors.forename: Deborah
authors.initials: D
authors.lastname: Brown
authors.forename: Ergin
authors.initials: E
authors.lastname: Ciftci
authors.forename: Patricia
authors.initials: P
authors.lastname: Contarini
authors.forename: Carl-Erik
authors.initials: CE
authors.lastname: Dempfle
authors.forename: Miroslav
authors.initials: M
authors.lastname: Dostalek
authors.forename: Susanne
authors.initials: S
authors.lastname: Eisert
authors.forename: Aslan
authors.initials: A
authors.lastname: Gökbuget
authors.forename: Omer
authors.initials: O
authors.lastname: Günhan
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Hidayat
authors.forename: Boris
authors.initials: B
authors.lastname: Hügle
authors.forename: Mete
authors.initials: M
authors.lastname: Isikoglu
authors.forename: Murat
authors.initials: M
authors.lastname: Irkec
authors.forename: Shelagh K
authors.initials: SK
authors.lastname: Joss
authors.forename: Sonja
authors.initials: S
authors.lastname: Klebe
authors.forename: Carolin
authors.initials: C
authors.lastname: Kneppo
authors.forename: Idil
authors.initials: I
authors.lastname: Kurtulus
authors.forename: Rakesh P
authors.initials: RP
authors.lastname: Mehta
authors.forename: Kemal
authors.initials: K
authors.lastname: Ornek
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schneppenheim
authors.forename: Stefan
authors.initials: S
authors.lastname: Seregard
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sweeney
authors.forename: Stephanie
authors.initials: S
authors.lastname: Turtschi
authors.forename: Gabor
authors.initials: G
authors.lastname: Veres
authors.forename: Petra
authors.initials: P
authors.lastname: Zeitler
authors.forename: Maike
authors.initials: M
authors.lastname: Ziegler
authors.forename: Volker
authors.initials: V
authors.lastname: Schuster
mesh_terms: D000818:Animals; D001778:Blood Coagulation Disorders / Q000235:genetics; D003231:Conjunctivitis / Q000209:etiology / Q000235:genetics; D005786:Gene Expression Regulation; D006580:Genetic Carrier Screening; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010958:Plasminogen / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D010958:Plasminogen