[Molecular genetic analysis for a pedigree with severe hereditary coagulation factor VII deficiency].
OBJECTIVE
To identify the genetic mutations of a severe inherited coagulation factor VII (FVII) deficiency pedigree.


METHODS
The diagnosis was validated by coagulant and haemostatic parameters. FVII gene mutations were screened in the propositus and his family members by DNA direct sequencing and confirmed by digestions of the restriction enzymes of the PCR production.


RESULTS
Two heterozygous missense mutations were found in the propositus of the pedigree: a G to T transversion at position 9482 in exon 6 and a C to T mutation at position 11348 in exon 8 resulting in the amino acid substitution of Arg152 with Leu and Arg304 with Trp, respectively. A heterozygous single nucleotide deletion (C) at position 11487-11489(CCC) within exon 8 was identified, which predicted the frameshift mutation at position His351 followed by the changes of six corresponding amino acids and appearance of a premature protein caused by stop codon. The heterozygous mutations identified in the proband were derived from his father (Arg152 to Leu) and his mother (Arg304 to Trp mutation) and a heterozygous deletion (C) at position 11487-9(CCC). By tracing the other pedigree members, it was found that his grandmother had a heterozygous mutation of Arg304Trp and a heterozygous polymorphism of Arg353Gln and his grandfather had a heterozygous Arg152Leu mutation.


CONCLUSIONS
Three heterozygous mutations were found in a pedigree with hereditary coagulation factor VII deficiency. Arg152Leu and deletion C at position 11487-9(CCC) were novel mutations.
Ding
Qiu-lan
QL
Shanghai Institute of Haematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Wang
Hong-li
HL
Wang
Xue-feng
XF
Wang
Ming-shan
MS
Fu
Qi-hua
QH
Wu
Wen-man
WM
Hu
Yi-qun
YQ
Wang
Zhen-yi
ZY
D000328:Adult; D000368:Aged; D001778:Blood Coagulation Disorders / Q000235:genetics*; D001780:Blood Coagulation Tests; D005167:Factor VII / Q000235:genetics*; D005168:Factor VII Deficiency / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation
D005167:Factor VII