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| Item Type: | Article |
|---|---|
| Title: | Familial thrombocytopenia due to a complex structural variant resulting in a WAC-ANKRD26 fusion transcript |
| Creators Name: | Wahlster, L., Verboon, J.M., Ludwig, L.S., Black, S.C., Luo, W., Garg, K., Voit, R.A., Collins, R.L., Garimella, K., Costello, M., Chao, K.R., Goodrich, J.K., DiTroia, S.P., O’Donnell-Luria, A., Talkowski, M.E., Michelson, A.D., Cantor, A.B. and Sankaran, V.G. |
| Abstract: | Advances in genome sequencing have resulted in the identification of the causes for numerous rare diseases. However, many cases remain unsolved with standard molecular analyses. We describe a family presenting with a phenotype resembling inherited thrombocytopenia 2 (THC2). THC2 is generally caused by single nucleotide variants that prevent silencing of ANKRD26 expression during hematopoietic differentiation. Short-read whole-exome and genome sequencing approaches were unable to identify a causal variant in this family. Using long-read whole-genome sequencing, a large complex structural variant involving a paired-duplication inversion was identified. Through functional studies, we show that this structural variant results in a pathogenic gain-of-function WAC-ANKRD26 fusion transcript. Our findings illustrate how complex structural variants that may be missed by conventional genome sequencing approaches can cause human disease. |
| Keywords: | Cell Line, Chromosome Breakage, Chromosome Disorders, Exome, HEK293 Cells, HeLa Cells, Intercellular Signaling Peptides and Proteins, Mutation, Pedigree, Signal Transducing Adaptor Proteins, Single Nucleotide Polymorphism, Thrombocytopenia, Tumor Cell Line |
| Source: | Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Volume: | 218 |
| Number: | 6 |
| Page Range: | e20210444 |
| Date: | 7 June 2021 |
| Official Publication: | https://doi.org/10.1084/jem.20210444 |
| PubMed: | View item in PubMed |
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