Biochemical activity and gene analysis of inherited protein C and antithrombin deficiency in two Chinese pedigrees.
BACKGROUND
We identified the gene mutations in two Chinese pedigree of type I hereditary protein C deficiency and type I hereditary antithrombin deficiency.


METHODS
The plasma level of protein C activity (PC:A), protein C antigen (PC:Ag), protein S activity, antithrombin activity (AT:A) and antithrombin antigen (AT:Ag) of propositi and two family members were detected using ELISA and chromogenic assay, respectively. All exons and intron-exon boundaries of protein C gene and antithrombin gene were analyzed by direct sequencing of the corresponding amplified PCR products in DNA from the propositus.


RESULTS
The plasma PC:A and PC:Ag of propositus 1 was 26% and 1.43 mg/dl, respectively. The PC:Ag and PC:A of his father were normal. The decreased PC:A level was seen in his mother and 4 of his maternal pedigree. PS:A and AT:A were all normal in pedigree 1 members. A C5498T heterozygous mutation in exon 3 of protein C gene, resulting in the substitution of Arg for Trp at the 15th amino acid, was identified in propositus 1 and 8 of his relatives. The plasma AT:A and AT:Ag of propositus 2 was 48.6% and 10.4 mg/dl, respectively. The reduced AT:A and AT:Ag levels were found in his father and 5 of paternal pedigree. PC:A, PC:Ag and PS:A were all in normal range. A heterozygous 13387-9G deletion in exon 6 of antithrombin gene was identified in propositus 2. This mutation introduced a frameshift and a premature stop at codon 426 and existed in 6 members of pedigree 2.


CONCLUSIONS
The C5498T heterozygous mutation in exon 3 of protein C gene, first reported in China, leads to type I hereditary protein C deficiency. The 13387-9G deletion, a novel mutation, can cause antithrombin deficiency and thrombosis.
Zhou
Rong-fu
RF
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Fu
Qi-hua
QH
Wang
Wen-bin
WB
Xie
Shuang
S
Hu
Yi-qun
YQ
Wang
Xue-feng
XF
Wang
Zhen-yi
ZY
Wang
Hong-li
HL
D000293:Adolescent; D002648:Child; D005260:Female; D005337:Fibrin / Q000172:deficiency*; D017353:Gene Deletion; D006801:Humans; D008297:Male; D010375:Pedigree; D011486:Protein C / Q000235:genetics; D020151:Protein C Deficiency / Q000235:genetics*
D011486:Protein C; D005337:Fibrin