title: Factor X Deficiency with Heterozygous Mutations of Novel p.G435S and Known p.G244R in a Patient Presenting with Severe Umbilical Hemorrhage.
abstract: A 10-day-old male patient was referred to our hospital with severe umbilical bleeding. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were prominently prolonged. Plasma coagulation factor X (FX) activity and antigen levels were 1% and 0.6%, respectively. A DNA sequence analysis of his leukocytes revealed a compound heterozygous state; known Gly244 to Arg (p.G244R) in exon 6 and a novel mutation of Gly 435 to Ser (p.G435S) in exon 8. A pedigree analysis showed that p.G244R originated from the paternal side, while p.G435S was from the maternal side. A p.G244R mutation was reported previously as FXDebrecenand this mutated protein was synthesized as a non-secretable protein. The glycine at amino acid position 435 in the C-terminal region is completely conserved in the trypsin-like serine protease family, including thrombin, FVII, protein C, plasmin, trypsin, and chymotrypsin. In a three-dimensional structural model of FX, Gly 435 was located within the 11thβ-strand and buried in the back of the catalytic pocket. Therefore, the substitution to serine was expected to disrupt this structure. p.G435S FX was also predicted to be synthesized and exist in the cytoplasm, but not to be secreted into culture media by a cDNA expression assay. These two mutations may be responsible for the type 1 (null levels of both activity and antigen in plasma) FX deficiency with severe bleeding phenotype.
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Matsuo
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Mizuochi
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Miho
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ozono
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sogabe
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Seki
authors.affiliation: R&D Department, The Chemo-Sero-Therapeutic Research Institute.
authors.forename: Kenji
authors.initials: K
authors.lastname: Soejima
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine.|Hematology and Oncology Center, St. Mary's Hospital.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine.
authors.forename: Yushiro
authors.initials: Y
authors.lastname: Yamashita
mesh_terms: D000596:Amino Acids; D001780:Blood Coagulation Tests; D005091:Exons; D005170:Factor X / Q000235:genetics*; D005171:Factor X Deficiency / Q000150:complications* / Q000235:genetics*; D005260:Female; D006470:Hemorrhage / Q000150:complications* / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010290:Parents; D010314:Partial Thromboplastin Time; D010375:Pedigree; D010641:Phenotype; D011487:Protein Conformation; D011517:Prothrombin Time; D014357:Trypsin / Q000737:chemistry; D014472:Umbilicus / Q000473:pathology*
chemical_list: D000596:Amino Acids; D005170:Factor X; D014357:Trypsin