Molecular and clinical spectrum of type I plasminogen deficiency: A series of 50 patients.
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.
Tefs
Katrin
K
Hospital for Children and Adolescents, University of Leipzig, Oststrasse 21-25, D-04317 Leipzig, Germany. katrin.tefs@medizin.uni-leipzig.de
Gueorguieva
Maria
M
Klammt
Jürgen
J
Allen
Carl M
CM
Aktas
Dilek
D
Anlar
Fehim Y
FY
Aydogdu
Sultan D
SD
Brown
Deborah
D
Ciftci
Ergin
E
Contarini
Patricia
P
Dempfle
Carl-Erik
CE
Dostalek
Miroslav
M
Eisert
Susanne
S
Gökbuget
Aslan
A
Günhan
Omer
O
Hidayat
Ahmed A
AA
Hügle
Boris
B
Isikoglu
Mete
M
Irkec
Murat
M
Joss
Shelagh K
SK
Klebe
Sonja
S
Kneppo
Carolin
C
Kurtulus
Idil
I
Mehta
Rakesh P
RP
Ornek
Kemal
K
Schneppenheim
Reinhard
R
Seregard
Stefan
S
Sweeney
Elizabeth
E
Turtschi
Stephanie
S
Veres
Gabor
G
Zeitler
Petra
P
Ziegler
Maike
M
Schuster
Volker
V
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
D010958:Plasminogen