@article{Victor B. Pastor_Sushree S. Sahoo_Jessica Boklan_Georg C. Schwabe_Ebru Saribeyoglu_Brigitte Strahm_Dirk Lebrecht_Matthias Voss_Yenan T. Bryceson_Miriam Erlacher_Gerhard Ehninger_Marena Niewisch_Brigitte Schlegelberger_Irith Baumann_John C. Achermann_Akiko Shimamura_Jochen Hochrein_Ulf Tedgård_Lars Nilsson_Henrik Hasle_Melanie Boerries_Hauke Busch_Charlotte M. Niemeyer_Marcin W. Wlodarski_2018, place={Pavia, Italy}, title={Constitutional SAMD9L mutations cause familial myelodysplastic syndrome and transient monosomy 7}, volume={103}, url={https://haematologica.org/article/view/8380}, DOI={10.3324/haematol.2017.180778}, abstractNote={Familial myelodysplastic syndromes arise from haploinsufficiency of genes involved in hematopoiesis and are primarily associated with early-onset disease. Here we describe a familial syndrome in seven patients from four unrelated pedigrees presenting with myelodysplastic syndrome and loss of chromosome 7/7q. Their median age at diagnosis was 2.1 years (range, 1–42). All patients presented with thrombocytopenia with or without additional cytopenias and a hypocellular marrow without an increase of blasts. Genomic studies identified constitutional mutations (p.H880Q, p.R986H, p.R986C and p.V1512M) in the <em>SAMD9L</em> gene on 7q21, with decreased allele frequency in hematopoiesis. The non-random loss of mutated <em>SAMD9L</em> alleles was attained via monosomy 7, deletion 7q, UPD7q, or acquired truncating <em>SAMD9L</em> variants p.R1188X and p.S1317RfsX21. Incomplete penetrance was noted in 30% (3/10) of mutation carriers. Long-term observation revealed divergent outcomes with either progression to leukemia and/or accumulation of driver mutations (n=2), persistent monosomy 7 (n=4), and transient monosomy 7 followed by spontaneous recovery with <em>SAMD9L</em>-wildtype UPD7q (n=2). Dysmorphic features or neurological symptoms were absent in our patients, pointing to the notion that myelodysplasia with monosomy 7 can be a sole manifestation of SAMD9L disease. Collectively, our results define a new subtype of familial myelodysplastic syndrome and provide an explanation for the phenomenon of transient monosomy 7. <em>Registered at: <a href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</a>; #<a class="external-ref external-ref-type-clintrialgov" href="/lookup/external-ref?link_type=CLINTRIALGOV&amp;access_num=NCT00047268&amp;atom=%2Fhaematol%2F103%2F3%2F427.atom">NCT00047268</a></em&gt;.}, number={3}, journal={Haematologica}, author={Victor B. Pastor and Sushree S. Sahoo and Jessica Boklan and Georg C. Schwabe and Ebru Saribeyoglu and Brigitte Strahm and Dirk Lebrecht and Matthias Voss and Yenan T. Bryceson and Miriam Erlacher and Gerhard Ehninger and Marena Niewisch and Brigitte Schlegelberger and Irith Baumann and John C. Achermann and Akiko Shimamura and Jochen Hochrein and Ulf Tedgård and Lars Nilsson and Henrik Hasle and Melanie Boerries and Hauke Busch and Charlotte M. Niemeyer and Marcin W. Wlodarski}, year={2018}, month={Feb.}, pages={427-437} }