골수형성이상증후군/급성골수성백혈병 환자에서 발견된 DDX41의 새로운 생식세포 돌연변이
A Novel Germline Mutation in DDX41 Predisposed to Myelodysplasia/Acute Myeloid Leukemia
동아대학교 의과대학 진단검사의학교실1, 동아대학교 의과대학 내과학교실 혈액종양내과2
Department of Laboratory Medicine1, Dong-A University College of Medicine, Busan; Division of Hematology and Oncology, Department of Internal Medicine2, Dong-A University College of Medicine, Busan, KoreaCorrespondence to:
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Lab Med Online 2022; 12(3): 209-213
Published July 1, 2022
Copyright © The Korean Society for Laboratory Medicine.
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) typically present as sporadic diseases. However, some cases of MDS or AML are associated with germline mutations harboring specific genetic and clinical characteristics [1, 2]. To date, 10 genes have been identified in familial MDS or AML:
MDS or AML with the germline
A 72-year-old woman presented to the emergency department with fever and general weakness. Complete blood count (CBC) results revealed pancytopenia with a hemoglobin (Hb) value of 9.2 g/dL, white blood cell (WBC) count of 1.50×109/L, and platelet count of 31×109/L. Peripheral blood smear (PBS) results revealed a few blasts without any dysplastic cells. A bone marrow smear revealed slightly hypocellular marrow with 16.2% leukemic blasts of all nucleated cells. The patient was diagnosed with myelodysplastic syndrome with excess blasts-2 (MDS-EB-2) displaying a normal karyotype. She started chemotherapy with decitabine because of a high-risk score evaluated (risk score 6.5) according to the revised International Prognostic Scoring System (IPSS-R) category . Following the 4th chemotherapy treatment, the PBS result showed no leukemic blasts with increased CBC parameters (Hb of 11.8 g/dL, WBC count of 2.70×109/L and platelet count of 143×109/L).
A follow-up bone marrow smear revealed normocellular marrow with 2.0% leukemic blasts of all nucleated cells, indicating complete remission. However, despite the 16th chemotherapy, pancytopenia persisted for 8 weeks. Moreover, leukemic myeloblasts (23.4% of all nucleated cells) were observed in the bone marrow sample, implying a transformation from MDS-EB-2 to AML. Chromosome analysis showed a normal karyotype in the follow-up studies. A multiplex nested reverse-transcription polymerase chain reaction analysis with HemaVision (DNA Diagnostic A/S, Risskov, Denmark), which enables the detection of 28 chromosomal rearrangements associated with acute leukemia, did not detect any rearrangement abnormalities. Targeted gene panel sequencing included AML-related 49 genes that were sequenced with MiSeq (Illumina, San Diego, CA, USA) according to manufacturer’s instructions. The sequencing results revealed the following: NM_000546.5:c.646G>A, p.(Val216Met), with an 8% variant allele frequency (VAF) of
The panel also detected one suspected germline variant, NM_016222.2:c.308_309del, p.(Glu103Valfs*31) of
Figure 1. (A) Family pedigree of the patient. The arrow indicates the proband. Circled dots indicate heterozygous carriers of the germline
DDX41p.(Glu103Valfs*31) variant. Child 2 and 3 refused genetic testing. (B) Electropherogram showing the germline heterozygous c.308_309del variant detected in the peripheral blood sample of the patient. (C) DDX41protein structure with germline DDX41variants reported in this case.
Some genetic predisposing factors for myeloid malignancies (e.g.,
The prognostic significance of myeloid neoplasms with germline
Germline alterations may cause predisposal to somatic mutations in the same gene . Similar to
In conclusion, we have identified a novel germline
Conflicts of Interest
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