학술논문
Homozygous intronic mutation leading to inefficient transcription combined with a novel frameshift mutation in F13A1 gene causes FXIII deficiency.
Document Type
Article
Author
Source
Subject
*BLOOD coagulation factor XIII
*GENETIC mutation
*GENETIC transcription
*GENETIC regulation
*NUCLEOTIDE sequence
*PROTEIN binding
*LUCIFERASES
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Language
ISSN
1434-5161
Abstract
Two novel mutations, 602-605delAAAG in exon 5 and Int1(+12)C>A, of the F13A1 gene were identified in a Chinese factor XIII (FXIII)-deficient family. The 602-605delAAAG mutation results in the premature termination of translation. To determine the functional effect of the Int1(+12)A mutation, we transiently expressed luciferase reporters in U937 cells. We found that the first 951 bp of F13A1 intron 1 is involved in regulating the expression of the F13A1 gene and that Int1(+12)A results in its reduced expression. Electrophoretic mobility shift assay indicated that Int1(+12)A causes reduced protein binding. An Sp1 site was predicted in the sequence containing Int1(+12)C, which the Int1(+12)A mutation eliminates. Co-transfection of a plasmid expressing Sp1 revealed that Sp1 is involved in regulating the expression of FXIIIA and that Int1(+12)A leads to inefficient transcription. These results provide the first insight into a novel regulatory mechanism involving intron 1 in the F13A1 gene. [ABSTRACT FROM AUTHOR]