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Case Reports
. 2017 Aug;31(8):1827-1830.
doi: 10.1038/leu.2017.142. Epub 2017 May 10.

Germline SAMD9 mutation in siblings with monosomy 7 and myelodysplastic syndrome

J R Schwartz  1 , S Wang  2 , J Ma  3 , T Lamprecht  3 , M Walsh  3 , G Song  3 , S C Raimondi  3 , G Wu  2 , M F Walsh  4 , R B McGee  1 , C Kesserwan  1 , K E Nichols  1 , B E Cauff  5 , R C Ribeiro  1 , M Wlodarski  6 , J M Klco  3
Affiliations
Case Reports

Germline SAMD9 mutation in siblings with monosomy 7 and myelodysplastic syndrome

J R Schwartz et al. Leukemia. 2017 Aug.
No abstract available

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Conflict of interest statement

Conflict of Interest Statement

The authors have nothing to disclose.

Figures

Figure 1
Figure 1. Diagnostic work up of 3 siblings with MDS and monosomy 7
A.) Bone marrow core biopsy and aspirate (inset) showing dysplastic megakaryocytes in Sibling 1. B.) Copy number analysis demonstrating monosomy 7 in myeloid cells all three siblings. C.) Smoothed color density plots of chromosome 7 B-allele frequency (BAF) of lymphocyte (normal) and myeloid (tumor) DNA in Sibling 3 showing a subclonal population with allelic imbalance, despite the lack of a copy number change, consistent with CN-LOH in the lymphocytes. Darker blue signifies a higher data point (SNP alternative allele frequencies) density. Red vertical line indicates genomic location of SAMD9 and SAMD9L.
Figure 2
Figure 2. Sequencing validation and biologic characterization of the SAMD9 p.E1136Q mutation
A.) Family pedigree identifying those with a SAMD9 mutation and their monosomy 7 status (filled: monosomy 7; open: untested karyotype). Ages at diagnosis are below pedigree symbols, bracketed numbers adjacent to karyotype below indicate fraction of metaphases affected. B.) Locations of mutations within the SAMD9 protein, a Sanger sequencing electropherogram (1-Reference, 2-Reverse primer) confirming the SAMD9 p.E1136Q mutation in the mother, and tumor/normal variant allele frequency (VAF) values for the p.E1136Q mutation. C.) Western blot (representative of multiple biological replicates) showing less ERK phosphorylation in 293T cells transiently expressing the mutant GFP-SAMD9 protein when compared to the wild-type at 0, 10, and 60 minutes following serum stimulation. The R1293W mutation was identified in some patients with MIRAGE syndrome (8). GFP indicates the empty GFP-fusion vector. The following antibodies were used: SAMD9: abcam (ab180575), From Cell Signaling Technologies: Total ERK (4695S), Phos-ERK (9101S), and GAPDH (2118S).
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References

    1. Wlodarski MW, Hirabayashi S, Pastor V, Stary J, Hasle H, Masetti R, et al. Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents. Blood. 2016;127(11):1387–97. quiz 518. - PubMed
    1. Babushok DV, Bessler M, Olson TS. Genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia in children and young adults. Leuk Lymphoma. 2016;57(3):520–36. - PMC - PubMed
    1. Shannon KM, Turhan AG, Chang SS, Bowcock AM, Rogers PC, Carroll WL, et al. Familial bone marrow monosomy 7. Evidence that the predisposing locus is not on the long arm of chromosome 7. J Clin Invest. 1989;84(3):984–9. - PMC - PubMed
    1. Carroll WL, Morgan R, Glader BE. Childhood bone marrow monosomy 7 syndrome: a familial disorder? J Pediatr. 1985;107(4):578–80. - PubMed
    1. Sakaguchi H, Okuno Y, Muramatsu H, Yoshida K, Shiraishi Y, Takahashi M, et al. Exome sequencing identifies secondary mutations of SETBP1 and JAK3 in juvenile myelomonocytic leukemia. Nat Genet. 2013;45(8):937–41. - PubMed

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