[Severe hereditary coagulation factor V deficiency caused by two novel heterozygous mutations].
OBJECTIVE
To identify 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 (FV:Ag) tests were performed for phenotypic diagnosis. The genomic DNA was extracted from the peripheral blood of the proband and all the 25 exons and their flanks of FV gene were amplified by polymerase chain reaction (PCR). The PCR products were screened by direct sequencing and the mutations were further confirmed by restriction enzyme digestion.


RESULTS
APTT, PT, TT, FV:C, FV:Ag of the proband were 249.2 s, 46.6 s, 17.9 s, 0.1% and 1.5%, respectively. FII, FVII, FVIII, FIX, FX activities, vWF and Fg were within normal ranges. Taking the GenBank Z99572 sequence as the reference, four mutations were identified in FV gene of the proband. They were a heterozygous two bases deletion in exon 13 (2238 approximately 2239delAG) introducing a frameshift and a premature stop at codon 689, and a heterozygous missense mutation in exon 23 (G6410T) resulting in the substitution of Gly for Val at codon 2079, respectively. The proband's father and mother were heterozygous for G6410T and for 2238 approximately 2239delAG, respectively.


CONCLUSIONS
The severe FV deficiency of the proband is caused by a frameshift mutation of 2238 approximately 2239delAG and a missense mutation of G6410T, which haven't been identified before.
Zhou
Rong-fu
RF
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Fu
Qi-hua
QH
Xu
Xiu-cai
XC
Wang
Wen-bin
WB
Wu
Wen-man
WM
Ding
Qiu-lan
QL
Xie
Shuang
S
Zhai
Zhi-min
ZM
Hu
Yi-qun
YQ
Wang
Xue-feng
XF
Wu
Jing-sheng
JS
Wang
Hong-li
HL
D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005165:Factor V / Q000235:genetics* / Q000378:metabolism; D005166:Factor V Deficiency / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D010314:Partial Thromboplastin Time; D010375:Pedigree; D010641:Phenotype; D011517:Prothrombin Time; D013918:Thrombin Time
C035876:factor V clotting antigen; D005165:Factor V