[Two novel factor V gene mutations associated with congenital coagulation factor V deficiency, study of one pedigree].
OBJECTIVE
To discover the gene mutations of a pedigree with inherited factor V (FV) deficiency.


METHODS
The activated partial thromboplastin time (APTT), prothrombin time (PT), FV activity (FV:C) and FV antigen test were adopted for phenotype diagnosis. The genomic DNA was extracted from the peripheral blood of the 16-year-old propositus, female. All the 25 exons and their flanks in the FV gene of the propositus were amplified by polymerase chain reaction (PCR). The PCR products were screened by direct sequencing and the mutations were further confirmed by restricted enzyme digestion. Six persons in the pedigree (grandfather, grandmother, father, mother, uncle, and aunt) were examined too. 108 healthy blood donors were used as controls.


RESULTS
The APTT, PT, FV:C, and FV:Ag of the propositus were 126.6s, 42.8s, 0.3% and 1.3% respectively. The Fbg and FII, FVII, FVIII, FIX, FX activities were in normal range. FV:C of the members of the pedigree was 36% - 70%, and the FV:Ag of the pedigree members was 26.4% - 45.3% that of the mixture of 30 normal plasma samples. Taking the GeneBank Z99572 sequence as the reference, totally five variations in the FV gene were found in the propositus. The mutations, A1348G and 4887 approximately 8delG, were traced to her father and her mother respectively. No 1348G-->T mutation was found in the 108 controls.


CONCLUSIONS
The FV deficiency of the propositus is caused by missense mutation of G1348T and frameshift mutation of 4887 approximately 8delG, which haven't been identified previously.
Fu
Qi-hua
QH
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Wang
Hong-li
HL
Wang
Ming-shan
MS
Ding
Qiu-lan
QL
Wu
Wen-man
WM
Hu
Yi-qun
YQ
Wang
Xue-feng
XF
Wang
Zhen-yi
ZY
D000293:Adolescent; D001483:Base Sequence; D005165:Factor V / Q000235:genetics*; D005166:Factor V Deficiency / Q000151:congenital* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree
D005165:Factor V