Whole Exome Sequencing Reveals Uncommon Mutations in the Recently Identified Fanconi Anemia Gene SLX4/FANCP |
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| Authors: | Chantal Stoepker Eunike Velleuer Richard Friedl Birgit Gottwald‐Mühlhauser Johan P. de Winter Detlev Schindler |
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| Affiliation: | 1. Department of Clinical Genetics, Vrije Universteit (VU) Medical Center, , Amsterdam, The Netherlands;2. Department of Pediatric Hematology, Oncology and Clinical Immunology, University of Duesseldorf School of Medicine, , Duesseldorf, Germany;3. Department of Human Genetics, University of Wuerzburg, , Wuerzburg, Germany |
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| 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. |
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| Keywords: | Fanconi anemia FANCP, SLX4 nuclear localization signal |
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