[A novel genetic defect in a Chinese family with inherited coagulation factor XIII deficiency].
OBJECTIVE
To identify the genetic defect of inherited coagulation factor (F) deficiency in a Chinese family and to explore its molecular mechanism.


METHODS
The activity and antigen of plasma F were measured by photometric test and enzyme-linked immunosorbent assay, and rocket-electrophoresis, respectively. All the exons and exon-intron boundaries of the FA subunit gene were amplified by PCR and then DNA sequencing was performed. Restriction endonuclease analysis was used for the PCR products of the family members and 80 healthy donors to exclude gene polymorphism.


RESULTS
Rapid dissolution of the proband's fibrin clot occurred within 30 minutes, and antigen of his plasma F was significantly decreased, two compound heterozygous missense mutations (a C to T transition at nucleotide 177,246 which caused Arg703Trp, and a A to G transition at nucleotide 177,286 which caused His716Arg) in exon 15 of FA subunit gene were found. The possibility of gene polymorphism was excluded by restriction endonuclease analysing. Each of these two missense mutations was respectively found in his mother and father. Molecular modeling based on 3D crystallographic data predicted that the mutant protein decreased stability and was likely to be rapidly degraded.


CONCLUSIONS
The inherited F deficiency in the Chinese family is caused by two compound heterozygous missense mutations-Arg703Trp and His716Arg in the FA subunit, which to our knowledge, are reported for the first time.
Wu
Shu-yan
SY
Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Wang
Zhao-yue
ZY
Dong
Ning-zheng
NZ
Zhang
Wei
W
Bai
Xia
X
Ruan
Chang-geng
CG
D001483:Base Sequence; D002648:Child; D005091:Exons; D005176:Factor XIII / Q000235:genetics*; D005177:Factor XIII Deficiency / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree
D005176:Factor XIII