Constitutional SAMD9L mutations cause familial myelodysplastic syndrome and transient monosomy 7

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Constitutional SAMD9L mutations cause familial myelodysplastic syndrome and transient monosomy 7. / Pastor, Victor B.; Sahoo, Sushree S.; Boklan, Jessica; Schwabe, Georg C.; Saribeyoglu, Ebru; Strahm, Brigitte; Lebrecht, Dirk; Voss, Matthias; Bryceson, Yenan T.; Erlacher, Miriam; Ehninger, Gerhard; Niewisch, Marena; Schlegelberger, Brigitte; Baumann, Irith; Achermann, John C.; Shimamura, Akiko; Hochrein, Jochen; Tedgård, Ulf; Nilsson, Lars; Hasle, Henrik; Boerries, Melanie; Busch, Hauke; Niemeyer, Charlotte M.; Wlodarski, Marcin W.

In: Haematologica, Vol. 103, No. 3, 28.02.2018, p. 427-437.

Research output: Contribution to journalArticle

Harvard

Pastor, VB, Sahoo, SS, Boklan, J, Schwabe, GC, Saribeyoglu, E, Strahm, B, Lebrecht, D, Voss, M, Bryceson, YT, Erlacher, M, Ehninger, G, Niewisch, M, Schlegelberger, B, Baumann, I, Achermann, JC, Shimamura, A, Hochrein, J, Tedgård, U, Nilsson, L, Hasle, H, Boerries, M, Busch, H, Niemeyer, CM & Wlodarski, MW 2018, 'Constitutional SAMD9L mutations cause familial myelodysplastic syndrome and transient monosomy 7', Haematologica, vol. 103, no. 3, pp. 427-437. https://doi.org/10.3324/haematol.2017.180778

APA

Pastor, V. B., Sahoo, S. S., Boklan, J., Schwabe, G. C., Saribeyoglu, E., Strahm, B., ... Wlodarski, M. W. (2018). Constitutional SAMD9L mutations cause familial myelodysplastic syndrome and transient monosomy 7. Haematologica, 103(3), 427-437. https://doi.org/10.3324/haematol.2017.180778

CBE

Pastor VB, Sahoo SS, Boklan J, Schwabe GC, Saribeyoglu E, Strahm B, Lebrecht D, Voss M, Bryceson YT, Erlacher M, Ehninger G, Niewisch M, Schlegelberger B, Baumann I, Achermann JC, Shimamura A, Hochrein J, Tedgård U, Nilsson L, Hasle H, Boerries M, Busch H, Niemeyer CM, Wlodarski MW. 2018. Constitutional SAMD9L mutations cause familial myelodysplastic syndrome and transient monosomy 7. Haematologica. 103(3):427-437. https://doi.org/10.3324/haematol.2017.180778

MLA

Vancouver

Pastor VB, Sahoo SS, Boklan J, Schwabe GC, Saribeyoglu E, Strahm B et al. Constitutional SAMD9L mutations cause familial myelodysplastic syndrome and transient monosomy 7. Haematologica. 2018 Feb 28;103(3):427-437. https://doi.org/10.3324/haematol.2017.180778

Author

Pastor, Victor B. ; Sahoo, Sushree S. ; Boklan, Jessica ; Schwabe, Georg C. ; Saribeyoglu, Ebru ; Strahm, Brigitte ; Lebrecht, Dirk ; Voss, Matthias ; Bryceson, Yenan T. ; Erlacher, Miriam ; Ehninger, Gerhard ; Niewisch, Marena ; Schlegelberger, Brigitte ; Baumann, Irith ; Achermann, John C. ; Shimamura, Akiko ; Hochrein, Jochen ; Tedgård, Ulf ; Nilsson, Lars ; Hasle, Henrik ; Boerries, Melanie ; Busch, Hauke ; Niemeyer, Charlotte M. ; Wlodarski, Marcin W. / Constitutional SAMD9L mutations cause familial myelodysplastic syndrome and transient monosomy 7. In: Haematologica. 2018 ; Vol. 103, No. 3. pp. 427-437.

RIS

TY - JOUR

T1 - Constitutional SAMD9L mutations cause familial myelodysplastic syndrome and transient monosomy 7

AU - Pastor, Victor B.

AU - Sahoo, Sushree S.

AU - Boklan, Jessica

AU - Schwabe, Georg C.

AU - Saribeyoglu, Ebru

AU - Strahm, Brigitte

AU - Lebrecht, Dirk

AU - Voss, Matthias

AU - Bryceson, Yenan T.

AU - Erlacher, Miriam

AU - Ehninger, Gerhard

AU - Niewisch, Marena

AU - Schlegelberger, Brigitte

AU - Baumann, Irith

AU - Achermann, John C.

AU - Shimamura, Akiko

AU - Hochrein, Jochen

AU - Tedgård, Ulf

AU - Nilsson, Lars

AU - Hasle, Henrik

AU - Boerries, Melanie

AU - Busch, Hauke

AU - Niemeyer, Charlotte M.

AU - Wlodarski, Marcin W.

PY - 2018/2/28

Y1 - 2018/2/28

N2 - 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 SAMD9L gene on 7q21, with decreased allele frequency in hematopoiesis. The non-random loss of mutated SAMD9L alleles was attained via monosomy 7, deletion 7q, UPD7q, or acquired truncating SAMD9L 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 SAMD9L-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. Registered at: www.clinicaltrials.gov; #NCT00047268.

AB - 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 SAMD9L gene on 7q21, with decreased allele frequency in hematopoiesis. The non-random loss of mutated SAMD9L alleles was attained via monosomy 7, deletion 7q, UPD7q, or acquired truncating SAMD9L 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 SAMD9L-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. Registered at: www.clinicaltrials.gov; #NCT00047268.

UR - http://www.scopus.com/inward/record.url?scp=85042784559&partnerID=8YFLogxK

U2 - 10.3324/haematol.2017.180778

DO - 10.3324/haematol.2017.180778

M3 - Article

VL - 103

SP - 427

EP - 437

JO - Haematologica-The Hematology Journal

T2 - Haematologica-The Hematology Journal

JF - Haematologica-The Hematology Journal

SN - 1592-8721

IS - 3

ER -