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.
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Acknowledgements
This work was supported by grants from the Natural Science Foundation of China (no. 30060037) and the National Ministry of Education (no. 03147). We thank Professor Akitada Ichinose and Dr Rashida Anwar for their helpful discussions. We also thank the patients and their family for their cooperation and support. We thank Drs DF Zhou, KJ Dong and GQ Zhang for their technical assistance.
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Wang, W., Huang, L., Ma, Q. et al. Homozygous intronic mutation leading to inefficient transcription combined with a novel frameshift mutation in F13A1 gene causes FXIII deficiency. J Hum Genet 56, 460–463 (2011). https://doi.org/10.1038/jhg.2011.41
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DOI: https://doi.org/10.1038/jhg.2011.41
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