Analysis of phenotype and genotype in two Chinese pedigrees with hereditary protein C deficiency.
- Author:
Xiao-Hong CAI
1
;
Rong-Fu ZHOU
;
Shuang XIE
;
Wen-Bin WANG
;
Jing DAI
;
Qiu-Lan DING
;
Yi FANG
;
Fei XIE
;
Xue-Feng WANG
;
Hong-Li WANG
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Asian Continental Ancestry Group; genetics; China; Female; Genotype; Humans; Male; Mutation; Pedigree; Phenotype; Polymorphism, Genetic; Protein C Deficiency; genetics
- From: Chinese Journal of Hematology 2007;28(3):147-151
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo identify the phenotype and gene mutation in two Chinese pedigrees with hereditary protein C deficiency.
METHODSThe plasma level of protein C activity (PC: A) , protein C antigen (PC: Ag), protein S activity (PS: A), and antithrombin activity (AT: A) of the probands and their family members were detected using chromogenic assay and ELISA, respectively. All of the nine exons and intron-exon boundaries of protein C gene were amplified by PCR and analyzed by direct sequencing of the probands. Restriction enzyme site analysis was used to confirm the mutation.
RESULTSThe plasma PC: A and PC: Ag for proband 1 was 1.2% and 0, respectively. Compound heterozygous mutations, C(TGC)64W (TGG) and F(TTC) 139V(GTC) , were identified in her, the former being inherited from the maternal side and the later the paternal side. Further genetic analysis showed that her husband ( II 8) had the heterozygous deletion mutation (K150 or 151 Del) in exon 7, her daughter had the same heterozygous deletion mutation and a F139V. The plasma PC: A and PC: Ag for proband 2 was 50. 3% and 1.9 mg/L, respectively. He had the heterozygous Lys150 or Lys151 deletion mutation, which was inherited from his father. Polymorphisms of C/T at position - 1654, A/G at - 1641 , and A/T at - 1476A/T in the promoter region of protein C were confirmed in all members of the two pedigrees, of which, proband 2 had homozygous CC/GG/TT. The F139V mutation was confirmed by restriction enzyme site analysis and polymorphism for this mutation was excluded. PS: A and AT: A were in normal range for all members.
CONCLUSIONCompound heterozygous mutation C64W and F139V of protein C gene lead to type I hereditary protein C deficiency for proband 1. K150 or 151 deletion mutation and polymorphism of CC/GG/TT might lead to type I hereditary protein C deficiency for proband 2. C64W is a novel mutation for protein C gene. F139V and K150 or 151 deletion mutation are reported for the first time in China.