[Type I hereditary protein C deficiency due to C5498T mutation in protein C gene].
OBJECTIVE
To identify the gene mutation in a Chinese pedigree of type I hereditary protein C deficiency.


METHODS
The plasma levels of protein C activity (PC:A), protein C antigen (PC:Ag), protein S activity, and anti-thrombin activity (AT:A) of the propositus, male, aged 7, and 11 members of the pedigree were detected using ELISA and chromogenic assay respectively. All of the nine exons and intron-exon boundaries of protein C gene of the propositus were analyzed by direct sequencing of the corresponding amplified PCR products in DNA from the propositus. Restriction enzyme site analysis was used to confirm the mutation.


RESULTS
The plasma concentrations of protein C activity and antigen of the propositus were 26% and 1.43 g/L respectively. The PC:Ag and PC:A of his father were normal. Decreased PC:A level was seen in his mother and 4 of his maternal pedigree. PS:A and AT:A were all normal in all of the pedigree members. A C5498T heterozygous mutation in exon 3, resulting in the substitution of Arg for Trp at the 15th amino acid, was identified in the propositus and 8 of his relatives. This mutation was confirmed by restriction enzyme site analysis. Mutations C/T at position 2405, A/G at position 2418, and A/T at position 2583 in the protein C promoter region were confirmed in the propositus and all members of the pedigree.


CONCLUSIONS
C5498T heterozygous mutation in exon 3 of protein C gene, first reported in China, leads to type I hereditary.
Zhou
Rong-fu
RF
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Wang
Hong-li
HL
Fu
Qi-hua
QH
Wang
Wen-bin
WB
Wu
Wen-man
WM
Ding
Qiu-lan
QL
Xie
Shuang
S
Hu
Yi-qun
YQ
Wang
Xue-feng
XF
Wang
Zhen-yi
ZY
D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D011486:Protein C / Q000032:analysis / Q000235:genetics*; D020151:Protein C Deficiency / Q000235:genetics*
D011486:Protein C