title: Identification of three novel plasminogen (PLG) gene mutations in a series of 23 patients with low PLG activity.
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.
authors.affiliation: Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klammt
authors.forename: Louise
authors.initials: L
authors.lastname: Kobelt
authors.forename: Dilek
authors.initials: D
authors.lastname: Aktas
authors.forename: Ismet
authors.initials: I
authors.lastname: Durak
authors.forename: Aslan
authors.initials: A
authors.lastname: Gokbuget
authors.forename: Quintin
authors.initials: Q
authors.lastname: Hughes
authors.forename: Murat
authors.initials: M
authors.lastname: Irkec
authors.forename: Idil
authors.initials: I
authors.lastname: Kurtulus
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Lapi
authors.forename: Hadas
authors.initials: H
authors.lastname: Mechoulam
authors.forename: Roberto
authors.initials: R
authors.lastname: Mendoza-Londono
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Palumbo
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Steitzer
authors.forename: Khalid F
authors.initials: KF
authors.lastname: Tabbara
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Ozbek
authors.forename: Neri
authors.initials: N
authors.lastname: Pucci
authors.forename: Talia
authors.initials: T
authors.lastname: Sotomayor
authors.forename: Marian
authors.initials: M
authors.lastname: Sturm
authors.forename: Tim
authors.initials: T
authors.lastname: Drogies
authors.forename: Maike
authors.initials: M
authors.lastname: Ziegler
authors.forename: Volker
authors.initials: V
authors.lastname: Schuster
mesh_terms: D001778:Blood Coagulation Disorders / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D006579:Heterozygote; D006801:Humans; D006849:Hydrocephalus / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008954:Models, Biological; D009154:Mutation; D010375:Pedigree; D010518:Periodontitis / Q000235:genetics; D010958:Plasminogen / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D010958:Plasminogen