title: A K19E missense mutation in the plasminogen gene is a common cause of familial hypoplasminogenaemia.
abstract: The prevalence of familial plasminogen deficiency in Scotland has recently been calculated at 2.9/1000. However, little is known of the molecular genetic background and the frequency of plasminogen gene mutations in most cases of inherited plasminogen deficiency. Having previously identified 28 unrelated subjects with familial plasminogen deficiency from a cohort of 9611 blood donors, we have now reviewed 19 of these 28 subjects and screened the plasminogen gene in 15 subjects with hypoplasminogenaemia (plus five relatives) and four subjects with dysplasminogenaemia for mutations and polymorphisms. A missense mutation K19E in the plasminogen gene was found in 13 of the 15 propositi with hypoplasminogenaemia, in one of these in a homozygous manner. In two subjects with hypoplasminogenaemia, two new mutations (P353A and R471X) were identified. These three different mutations, if inherited in a homozygous or compound-heterozygous manner, may be associated with the development of ligneous conjunctivitis. In four subjects with dysplasminogenaemia, three heterozygous mutations (C548G, n = 1; A601T, n = 1; G693R, n = 2) were found. None of the propositi with plasminogen deficiency developed venous thrombosis at any time. In conclusion, the K19E mutation in the plasminogen gene is a common cause of hypoplasminogenaemia in Scotland, with an estimated prevalence of around 0.14%.
authors.affiliation: Children's Hospital, University of Leipzig, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Tefs
authors.forename: Campbell R
authors.initials: CR
authors.lastname: Tait
authors.forename: Isobel D
authors.initials: ID
authors.lastname: Walker
authors.forename: Nicole
authors.initials: N
authors.lastname: Pietzsch
authors.forename: Maike
authors.initials: M
authors.lastname: Ziegler
authors.forename: Volker
authors.initials: V
authors.lastname: Schuster
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006402:Hematologic Diseases / Q000097:blood / Q000151:congenital / Q000235:genetics*; D006487:Hemostasis / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010958:Plasminogen / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D010958:Plasminogen