Both authors contributed equally to this work.
1098-1004/asset/HUMU_left.gif?v=1&s=4065e12063da1c0efe3c1a74d4f13c3cd92fba18)
1098-1004/asset/HUMU_right.gif?v=1&s=58026811b6aa5bee5a3d0e0563a705f8b681f34d)
Brief Report
You have free access to this content
Whole Exome Sequencing Reveals Uncommon Mutations in the Recently Identified Fanconi Anemia Gene SLX4/FANCP
Article first published online: 16 OCT 2012
DOI: 10.1002/humu.22221
© 2012 Wiley Periodicals, Inc.
Additional Information
How to Cite
Schuster, B., Knies, K., Stoepker, C., Velleuer, E., Friedl, R., Gottwald-Mühlhauser, B., de Winter, J. P. and Schindler, D. (2013), Whole Exome Sequencing Reveals Uncommon Mutations in the Recently Identified Fanconi Anemia Gene SLX4/FANCP. Hum. Mutat., 34: 93–96. doi: 10.1002/humu.22221
- †
Both authors contributed equally to this work.
Contract grant sponsors: Schroeder-Kurth Fund at the University of Wuerzburg.
Communicated by Georgia Chenevix-Trench
Publication History
- Issue published online: 20 DEC 2012
- Article first published online: 16 OCT 2012
- Accepted manuscript online: 3 OCT 2012 04:20AM EST
- Manuscript Accepted: 7 SEP 2012
- Manuscript Received: 6 JUN 2012
Funded by
- Schroeder-Kurth Fund at the University of Wuerzburg
Keywords:
- Fanconi anemia;
- FANCP, SLX4;
- nuclear localization signal
ABSTRACT
Fanconi anemia (FA) is a rare genetic disorder characterized by congenital malformations, progressive bone marrow failure (BMF), and susceptibility to malignancies. FA is caused by biallelic or hemizygous mutations in one of 15 known FA genes, whose products are involved in the FA/BRCA DNA damage response pathway. Here, we report on a patient with previously unknown mutations of the most recently identified FA gene, SLX4/FANCP. Whole exome sequencing (WES) revealed a nonsense mutation and an unusual splice site mutation resulting in the partial replacement of exonic with intronic bases, thereby removing a nuclear localization signal. Immunoblotting detected no residual SLX4 protein, which was consistent with abrogated interactions with XPF/ERCC1 and MUS81/EME1. This cellular finding did not result in a more severe clinical phenotype than that of previously reported FA-P patients. Our study additionally exemplifies the versatility of WES for the detection of mutations in heterogenic disorders such as FA.