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Case Reports
. 2019 Jul;104(7):e318-e321.
doi: 10.3324/haematol.2018.207316. Epub 2019 Mar 28.

A novel germline SAMD9L mutation in a family with ataxia-pancytopenia syndrome and pediatric acute lymphoblastic leukemia

Jesse J C Cheah  1   2   3 , Anna L Brown  1   2   3   4 , Andreas W Schreiber  5   6 , Jinghua Feng  6 , Milena Babic  1 , Sarah Moore  1 , Chun-Chun Young  1 , Miriam Fine  7 , Kerry Phillips  7 , Michael Guandalini  8 , Peter Wilson  9 , Nicola Poplawski  4   7 , Christopher N Hahn  1   2   3   10 , Hamish S Scott  11   2   3   5   6   10
Affiliations
Case Reports

A novel germline SAMD9L mutation in a family with ataxia-pancytopenia syndrome and pediatric acute lymphoblastic leukemia

Jesse J C Cheah et al. Haematologica. 2019 Jul.
No abstract available

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Figures

Figure 1.
Figure 1.
Four generations of a family with ataxia pancytopenia syndrome and germline mutation of SAMD9L. (A) Germline p.Ser1473Asn mutation segregates with affected individuals. Additional somatic mutations and chromosomal aberrations (red text). Thr: thrombocytopenia; Macr: macrocytosis; AA: aplastic anemia; Atax: ataxia; cnLOH: copy neutral loss of heterozygosity; dx: age at diagnosis; a: age at last date of contact (years); d: age at death (years). (B) Axial and coronal T2 weighted magnetic resonance imaging (MRI) images of the brain of individual IV-4 with ataxia indicate symmetrical bilateral periventricular white matter hyperintensity (white arrows) and small rounded focal areas of hyperintense T2 signal which suppressed on FLAIR (not shown) suggestive of parenchymal cysts or prominent perivascular spaces (red arrows). (C) Sanger sequencing confirmation of heterozygous germline mutation SAMD9L S1473N (chr7:g.92760867C>T; c.4418G>A [NM_152703.4]; p.Ser1473Asn [NP_689916.2]) in hair and in peripheral blood mononuclear cells (PBMNC) of IV-2 indicates reduced variant allele load of mutant. (D) SNP-array of chromosome 7 of IV-2 shows cnLOH of 7q. The cnLOH of the long arm in IV-2 includes the SAMD9L gene in approximately 30% of cells. (E) Somatic frameshift mutation SAMD9L E461Vfs*43 (chr7:g.92763904_92763907delCTTT; c.1382_1385delAAAG; p.Glu461Val*43) was acquired by IV-2 with an allele load of approximately 38% while somatic frameshift mutation SAMD9L S608Tfs*6 (chr7:g.92763465_92763466dupTG; c.1821_1822dupCA; p.Ser608Thr*6) was acquired in IV-1 with an allele load of approximately 30%. Samples: IV-1: lymphoblastoid cell lines (LCL); IV-2: PBMNC. (F) Comparison of germline mutations in paralogous genes SAMD9L and SAMD9. #: identified in our study; underlined: germline mutations with other SAMD9L/SAMD9 somatic or germline mutations (in cis or biallelic). For full variant reference list, see Online Supplementary Tables S3 and S4. Percent conservation between proteins is shown (brackets show % identity).
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References

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