title: Identification of simultaneous mutation of fibrinogen alpha chain and protein C genes in a Japanese kindred.
abstract: Afibrinogenaemia usually induces a bleeding tendency during infancy, whereas protein C deficiency increases susceptibility to thrombosis in children or adolescence. Mutations of these genes have been, therefore, established as independent risk factors for coagulation disorders. We describe the homozygous mutation of the fibrinogen alpha chain gene and additional heterozygous mutation of the protein C gene in a male infant who showed prolonged umbilical bleeding after birth. On examination, the plasma fibrinogen was undetectable, and the activity and antigen level of protein C were reduced. The patient showed no fibrinogen Aalpha chain as well as Bbeta and gamma chains by Western blotting. The sequencing analysis showed the homozygous deletion of 1238 bases from intron 3 at position 2008 to intron 4 at position 3245 in the fibrinogen alpha chain gene. Both parents were heterozygous carriers of this mutation. In this patient, an additional mutation was also detected in the protein C gene: the heterozygous deletion of exon 7 at position 6161-6163 or 6164-6166, resulting the deletion of one amino acid (Lys150 or 151). His mother was also a carrier of this mutation. As the simultaneous mutation of the fibrinogen alpha chain and protein C genes has not been previously reported, the influence of the interaction between these two mutations on the clinical manifestations of this patient should be carefully monitored for a long period.
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Watanabe
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shibuya
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
authors.forename: Masako
authors.initials: M
authors.lastname: Kurihara
authors.forename: Sumiko
authors.initials: S
authors.lastname: Inoue
authors.forename: Miyuki
authors.initials: M
authors.lastname: Ono
authors.forename: Yui
authors.initials: Y
authors.lastname: Wada
authors.forename: Machiko
authors.initials: M
authors.lastname: Wakiyama
authors.forename: Masafumi
authors.initials: M
authors.lastname: Zaitsu
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iida
authors.forename: Kenji
authors.initials: K
authors.lastname: Muraoka
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kinoshita
authors.forename: Naotaka
authors.initials: N
authors.lastname: Hamasaki
mesh_terms: D000347:Afibrinogenemia / Q000097:blood / Q000235:genetics; D001778:Blood Coagulation Disorders / Q000097:blood / Q000235:genetics*; D001780:Blood Coagulation Tests; D015139:Blotting, Southern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005340:Fibrinogen / Q000235:genetics*; D017353:Gene Deletion; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D016133:Polymerase Chain Reaction; D011486:Protein C / Q000235:genetics*; D020151:Protein C Deficiency / Q000097:blood / Q000235:genetics
chemical_list: D017931:DNA Primers; D011486:Protein C; D005340:Fibrinogen