Analysis of an inherited FVII deficiency pedigree caused by homozygosity of Thr359Met.
- Author:
Hai-yan CHU
1
;
Hong-li WANG
;
Qiu-lan DING
;
Xue-feng WANG
;
Bin QU
;
Fang WU
;
Wen-ying KANG
;
Bao-hua DUAN
;
Jun YIN
;
Qi-hua FU
;
Wen-man WU
;
Zhen-yi WANG
Author Information
- Publication Type:Journal Article
- MeSH: Adolescent; Adult; Aged; DNA Mutational Analysis; Factor VII; genetics; Factor VII Deficiency; genetics; Female; Homozygote; Humans; Male; Middle Aged; Mutation, Missense; Pedigree; Polymerase Chain Reaction
- From: Chinese Journal of Hematology 2003;24(3):134-137
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the gene mutation type of an inherited coagulation factor VII deficiency pedigree.
METHODSFVII: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.
RESULTSHomozygosity 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.
CONCLUSIONSHomozygous 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.