title: A large deletion of the PROS1 gene in a deep vein thrombosis patient with protein S deficiency.
abstract: Inherited deficiency of protein S encoded by the PROS1 gene constitutes an important risk factor for deep vein thrombosis (DVT). Nevertheless, although more than 200 deleterious genetic variations in PROS1 have been identified, causative point mutations of PROS1 gene are not detected in approximately half of protein S-deficient families. The present study investigated whether there may exist a large deletion in PROS1 that constitutes a genetic risk factor for Japanese DVT patients. A multiplex ligation-dependent probe amplification analysis was employed to identify the deletions in PROS1 in 163 Japanese patients with DVT. A large gene deletion was identified in one patient who showed 16% protein S activity and did not carry point mutations in PROS1 by DNA sequencing and it was validated by the quantitative PCR method. The deletion spanned at least the whole PROS1 gene (107 kb) and at most from the centromere located downstream of PROS1, to before the D3S3619 marker, the first heterozygous marker in the upstream of PROS1 in chromosome 3. In conclusion, a large deletion in PROS1 was shown to partly account for DVT with protein S deficiency. Screening for large deletions in PROS1 might be warranted in PROS1 causative point mutation-negative DVT patients with protein S deficiency.
authors.affiliation: Research Institute, National Cardiovascular Center, Osaka, Japan.
authors.forename: Tong
authors.initials: T
authors.lastname: Yin
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeshita
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sato
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakata
authors.forename: Yongchol
authors.initials: Y
authors.lastname: Shin
authors.forename: Shigenori
authors.initials: S
authors.lastname: Honda
authors.forename: Tomio
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Hajime
authors.initials: H
authors.lastname: Tsuji
authors.forename: Tetsuhito
authors.initials: T
authors.lastname: Kojima
authors.forename: Seiji
authors.initials: S
authors.lastname: Madoiwa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakata
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Murata
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
mesh_terms: D000328:Adult; D001798:Blood Proteins / Q000235:genetics*; D002503:Centromere / Q000648:ultrastructure; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D007564:Japan; D008297:Male; D018895:Microsatellite Repeats; D008957:Models, Genetic; D017354:Point Mutation; D017293:Protein S; D018455:Protein S Deficiency / Q000235:genetics*; D012307:Risk Factors; D020246:Venous Thrombosis / Q000208:ethnology / Q000235:genetics*
chemical_list: D001798:Blood Proteins; C523390:PROS1 protein, human; D017293:Protein S