title: Genotype and laboratory and clinical phenotypes of protein s deficiency.
abstract: The diagnosis of thrombophilia caused by protein S deficiency remains difficult. From 2005 to 2010, we documented 135 patients with suspected hereditary protein S deficiency for whom mutational analysis of the PROS1 gene had been performed by direct double-stranded sequencing of the amplified 15 exons including splice sites. Multiplex ligation-dependent probe amplification was performed on 12 of 15 exons in cases with no mutation found but a large deletion in the PROS1 gene was suspected. Mutations were identified in 49 patients, 9 by familial screening. Altogether, 17 new and 11 previously described mutations of PROS1 were identified among the 49 patients. After the exclusion of acquired protein S deficiency due to pregnancy or hormonal contraceptives, there remained only 1 case with protein S activity levels less than 40% that could not be explained by sequence variations or deletions in the examined regions of the PROS1 gene. After the exclusion of conditions associated with acquired protein S deficiency, persistently low protein S activity levels are highly indicative of a genetic alteration in PROS1. We observed a clear correlation between the laboratory phenotype and the type of mutation.
authors.affiliation: Hemostasis Outpatient Clinics, Munich University Hospital, Ziemssenstrasse 1, Munich, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Duebgen
authors.forename: Teresa
authors.initials: T
authors.lastname: Kauke
authors.forename: Christoph
authors.initials: C
authors.lastname: Marschall
authors.forename: Andreas
authors.initials: A
authors.lastname: Giebl
authors.forename: Susanne
authors.initials: S
authors.lastname: Lison
authors.forename: Christina
authors.initials: C
authors.lastname: Hart
authors.forename: Andrea
authors.initials: A
authors.lastname: Dick
authors.forename: Michael
authors.initials: M
authors.lastname: Spannagl
mesh_terms: D001798:Blood Proteins / Q000172:deficiency* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D006801:Humans; D009154:Mutation; D017293:Protein S; D018455:Protein S Deficiency / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D019851:Thrombophilia / Q000097:blood / Q000175:diagnosis / Q000235:genetics*
chemical_list: D001798:Blood Proteins; C523390:PROS1 protein, human; D017293:Protein S