@article{34c2c16f836f4d539cecae28befec0e3,
title = "Familial thrombocytopenia due to a complex structural variant resulting in a WAC-ANKRD26 fusion transcript",
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.",
author = "Lara Wahlster and Verboon, {Jeffrey M.} and Ludwig, {Leif S.} and Black, {Susan C.} and Wendy Luo and Kopal Garg and Voit, {Richard A.} and Collins, {Ryan L.} and Kiran Garimella and Maura Costello and Chao, {Katherine R.} and Goodrich, {Julia K.} and DiTroia, {Stephanie P.} and Anne O{\textquoteright}Donnell-Luria and Talkowski, {Michael E.} and Michelson, {Alan D.} and Cantor, {Alan B.} and Sankaran, {Vijay G.}",
note = "Funding Information: This work was supported by a gift from the Lodish Family to Boston Children{\textquoteright}s Hospital, the New York Stem Cell Foundation, and National Institutes of Health grants R01 DK103794 and R01 HL146500 (to V.G. Sankaran). Funding for sequencing was partially provided by the Broad Institute of Massachusetts Institute of Technology and Harvard Center for Mendelian Genomics and was funded by the National Human Genome Research Institute, National Eye Institute, and National Heart, Lung, and Blood Institute grant UM1 HG008900 and by National Human Genome Research Institute grant R01 HG009141. The BLUEPRINT project data used was funded by the European Union{\textquoteright}s Seventh Framework Programme (FP7/ 2007-2013) under grant agreement no. 282510. V.G. Sankaran is a New York Stem Cell Foundation Robertson Investigator. Publisher Copyright: {\textcopyright} 2021 Wahlster et al.",
year = "2021",
month = apr,
day = "15",
doi = "10.1084/jem.20210444",
language = "English (US)",
volume = "218",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "6",
}