title: Complement factor H mutation in familial thrombotic thrombocytopenic purpura with ADAMTS13 deficiency and renal involvement.
abstract: Thrombotic thrombocytopenic purpura is a rare disorder of small vessels that is associated with deficiency of the von Willebrand factor-cleaving protease ADAMTS13, which favors platelet adhesion and aggregation in the microcirculation. The disease manifests mainly with central nervous system symptoms, but cases of renal insufficiency have been reported. Presented are findings of the genetic basis of phenotype heterogeneity in thrombotic thrombocytopenic purpura in two sisters within one family. The patients had ADAMTS13 deficiency as a result of two heterozygous mutations (causing V88M and G1239V changes). In addition, a heterozygous mutation (causing an S890I change) in factor H of complement was found in the patient who developed chronic renal failure but not in her sister, who presented with exclusive neurologic symptoms.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases, Aldo e Cele Daccò, Villa Camozzi-Ranica, Via Gavazzeni 11, 24125 Bergamo, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Noris
authors.forename: Sara
authors.initials: S
authors.lastname: Bucchioni
authors.forename: Miriam
authors.initials: M
authors.lastname: Galbusera
authors.forename: Roberta
authors.initials: R
authors.lastname: Donadelli
authors.forename: Elena
authors.initials: E
authors.lastname: Bresin
authors.forename: Federica
authors.initials: F
authors.lastname: Castelletti
authors.forename: Jessica
authors.initials: J
authors.lastname: Caprioli
authors.forename: Simona
authors.initials: S
authors.lastname: Brioschi
authors.forename: Friedrich
authors.initials: F
authors.lastname: Scheiflinger
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D017242:Complement Factor H / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics*; D008666:Metalloendopeptidases / Q000172:deficiency / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000150:complications / Q000235:genetics*
chemical_list: C493495:CFH protein, human; D017242:Complement Factor H; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human