[Analysis of an inherited FVII deficiency pedigree caused by homozygosity of Thr359Met].
OBJECTIVE
To explore the gene mutation type of an inherited coagulation factor VII deficiency pedigree.


METHODS
FVII:Ag, FVII:C, FVIIa were detected to classify deficiency type. FVII gene mutations were analysed in the proband and her family members by DNA directly sequencing. Biostructural pathology of the identified mutation was analysed by molecular modeling.


RESULTS
Homozygosity of C-->T transition at position 11514 in exon 8 resulting in Thr359Met was identified in the proband, and heterozygosity for Thr359Met was confirmed in her parents, her son and some other family members. Thr359Met induces CRM-deficiency. It is found by computer simulated molecular model that the replacement of Thr by Met which has a larger and longer side chain might cause steric hindrance, and change the number of H-bonds.


CONCLUSIONS
Homozygous missense mutation Thr359Met was found in a pedigree of hereditary FVII deficiency. This mutation might change the configuration of protein molecule and result in severe FVII deficiency.
Chu
Hai-yan
HY
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Wang
Hong-li
HL
Ding
Qiu-lan
QL
Wang
Xue-feng
XF
Qu
Bin
B
Wu
Fang
F
Kang
Wen-ying
WY
Duan
Bao-hua
BH
Yin
Jun
J
Fu
Qi-hua
QH
Wu
Wen-man
WM
Wang
Zhen-yi
ZY
D000293:Adolescent; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005167:Factor VII / Q000235:genetics*; D005168:Factor VII Deficiency / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction
D005167:Factor VII