[Double heterozygous mutations of non-canonical splice (IVS1a + 5g > a) and His348Gln caused inherited coagulation factor VII deficiency].
OBJECTIVE
To investigate the pathogenesis of inherited coagulation factor VII (FVII) deficiency.


METHODS
The diagnosis was validated by coagulant parameter assay. FVII gene mutations were analysed in the proband by DNA direct sequencing of PCR products of all exons, exon-intron boundaries and the 3', 5'untranslated sequences. The mutations were confirmed by reverse sequencing. The ectopic transcripts of RT-PCR were used to confirm the characteristics of the mutation in non-canonical splice site (IVS1a + 5g > a).


RESULTS
Double heterozygous mutations in the propositus were identified: a T to G mutation at position 10961, resulting in His348Gln substitution, a non-canonical splice site (IVS1a + 5g > a) mutation, causing the new model of splice and frameshift mutation.


CONCLUSIONS
Double heterozygous mutations of His348Gln and IVS1a + 5g > a were identified in a propositus, the splicing pattern of the IVS1a + 5g > a mutation was reported for the first time.
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
D000595:Amino Acid Sequence; D001483:Base Sequence; D005167:Factor VII / Q000235:genetics*; D005168:Factor VII Deficiency / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D012326:RNA Splicing
D005167:Factor VII