Perinatal-lethal nonimmune fetal hydrops attributed to MECOM-associated bone marrow failure.

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cold Spring Harbor Molecular Case Studies Pub Date : 2023-06-01 DOI:10.1101/mcs.a006289
Camille A Dash, Jill A Madden, Christy Cummings, Melissa Rose, Sheria D Wilson, Mari Mori, Pankaj B Agrawal, Bimal P Chaudhari, Monica H Wojcik
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Abstract

Pathogenic variants in MECOM, a gene critical to the self-renewal and proliferation of hematopoietic stem cells, are known to cause a rare bone marrow failure syndrome associated with amegakaryocytic thrombocytopenia and bilateral radioulnar synostosis known as RUSAT2. However, the spectrum of disease seen with causal variants in MECOM is broad, ranging from mildly affected adults to fetal loss. We report two cases of infants born preterm who presented at birth with symptoms of bone marrow failure including severe anemia, hydrops, and petechial hemorrhages; radioulnar synostosis was not observed in either patient, and, unfortunately, neither infant survived. In both cases, genomic sequencing revealed de novo variants in MECOM considered to be responsible for their severe presentations. These cases add to the growing body of literature that describe MECOM-associated disease, particularly MECOM as a cause of fetal hydrops due to bone marrow failure in utero. Furthermore, they support the use of a broad sequencing approach for perinatal diagnosis, as MECOM is absent from available targeted gene panels for hydrops, and highlight the importance of postmortem genomic investigation.

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由mecom相关骨髓衰竭引起的围产期致死性非免疫性胎儿水肿。
MECOM是一种对造血干细胞自我更新和增殖至关重要的基因,已知其致病变异可导致一种罕见的骨髓衰竭综合征,与单核细胞血小板减少症和双侧尺桡关节闭锁有关。然而,在MECOM的因果变异中看到的疾病范围很广,从轻度影响的成年人到胎儿丢失。我们报告两例早产婴儿出生时出现骨髓衰竭症状,包括严重贫血、水肿和点状出血;两名患者均未观察到尺桡关节粘连,不幸的是,两名婴儿均未存活。在这两种情况下,基因组测序显示MECOM的新生变异被认为是导致其严重表现的原因。这些病例增加了越来越多的文献描述MECOM相关疾病,特别是MECOM是由于子宫内骨髓衰竭导致胎儿水肿的原因。此外,他们支持使用广泛的测序方法进行围产期诊断,因为MECOM在现有的积水靶向基因面板中缺失,并强调了死后基因组调查的重要性。
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来源期刊
Cold Spring Harbor Molecular Case Studies
Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.20
自引率
0.00%
发文量
54
期刊介绍: Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.
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