{
  "abstract": "Background: Inherited bone marrow failure syndromes (IBMFS) show a significant association and overlap with inborn errors of immunity (IEI), manifesting as cytopenias, recurrent infections, hemophagocytic lymphohistiocytosis (HLH), and predisposition to myeloid neoplasms. SAMD9 and SAMD9L cause roughly 8% to 20% of pediatric myelodysplastic syndrome (MDS) cases. These mutations impair cell growth and frequently lead to high-risk monosomy 7, rapid progression to acute myeloid leukemia. Case report: Female patient, 1 year and 11 months old, daughter of non-consanguineous parents, with a family history of death of a brother at 1 year and 9 months due to pulmonary sepsis, later identified with hypogammaglobulinemia. She was referred for immunological investigation due to recurrent upper respiratory tract infections and a previous episode of pneumonia. In May 2026, she was admitted to the ICU after a rash 15 days ago, which progressed to runny nose, nasal obstruction and cough and severe afebrile pancytopenia. Virus serology revealed positive IgG for Parvovirus and positive IgM for Dengue. Negative for EBV, CMV, HIV and hepatitis. Biopsy as well as aspiration puncture of the BM showed severe hypocellularity and hemophagocytosis; hyperferritinemia (1,850 ng/mL), hypertriglyceridemia (248 mg/dL) and soluble IL-2 receptor of 42,094 pg/mL (VR < 3,900), meeting criteria for HLH. The immunological evaluation showed a reduction in IgG and IgM immunoglobulins, T cell compartment was preserved. The DEB test was negative. Conventional karyotyping and FISH analysis on bone marrow cells showed 45,XX,-7[11]/46,XX[3] and 45,XX,ish.-7[9], respectively, consistent with monosomy 7. Whole-genome sequencing identified the heterozygous germline variant *SAMD9L* c.4648T>C, p.(Ser1550Pro), classified as a variant of uncertain significance (VUS). The diagnosis was MDS-HLH. The patient was treated with antibiotics, red blood cell transfusions, dexamethasone, and immunoglobulin, showing a slow but satisfactory response; HLA typing was performed, and she was registered with REREME for a bone marrow transplant. Discussion: This case illustrates the complex interface between inborn errors of immunity (IEI), IBMFS, and germline predisposition to MDS. Alterations in SAMD9L exert an antiproliferative effect on hematopoietic cells, favoring adaptive events such as the loss of chromosome 7—a mechanism linked to the predisposition for MDS Although the identified variant remains classified as a VUS, the constellation of clinical, immunological, cytogenetic, and molecular findings supports a strong association between the germline alteration and the clinical presentation. Conclusion: This important report reinforces that children presenting with an infectious condition that progresses to pancytopenia, bone marrow hypocellularity due to hemophagocytosis, and hyperferritinemia are exhibiting HLH; a familial origin should be suspected, particularly if associated with immunodeficiency and monosomy 7. Although the SAMD9L variant is currently classified as a VUS, the rarity of such cases means the full clinical and laboratory spectrum remains to be defined; this allows for future reclassification, thereby contributing to a definitive diagnosis, therapeutic decision-making, monitoring of clonal evolution, and familial genetic counseling.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Images, Hematology, and Oncology, Faculdade de Medicina de Ribeirao Preto (FMRP), Universidade de São Paulo (USP), São Paulo, SP, Brazil",
    "Department of Pediatric Oncology, Hospital Português, Recife, PE, Brazil",
    "Infectious Diseases Service, Hospital Universitário Oswaldo Cruz (HUOC), Universidade de Pernambuco (UPE), Recife, PE, Brazil",
    "Pediatric Oncohematology Center (CEONHPE), Hospital Universitário Oswaldo Cruz (HUOC), Universidade de Pernambuco (UPE), Recife, PE, Brazil",
    "Cytogenetics Laboratory, Cell and Gene Therapy Program, Instituto Nacional de Câncer (INCA), Recife, PE, Brazil"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Matheus Do Nascimento CARVALHO"
    },
    {
      "affs": [
        1
      ],
      "name": "Daniely Feitoza SANTOS"
    },
    {
      "affs": [
        1
      ],
      "name": "Débora Costa Franco ROCHA"
    },
    {
      "affs": [
        2
      ],
      "name": "Ana Carla Augusto Moura FALCÃO"
    },
    {
      "affs": [
        3
      ],
      "name": "Maria Luiza Rosa BORGES"
    },
    {
      "affs": [
        4
      ],
      "name": "Teresa de Souza FERNANDEZ"
    },
    {
      "affs": [
        3
      ],
      "name": "Terezinha de Jesus Marques SALLES"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/de5hx47qw0y9s.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.107951",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926016986",
  "id": "de5hx47qw0y9s",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.107951",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC633-647.5"
    ],
    [
      "openalex",
      "2720|Autoimmune and Inflammatory Disorders Research"
    ]
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  "openalex": "W7223121840",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/de5hx47qw0y9s.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:35Z",
      "native_id": "8f9ad0ec78d443d1a9eae29d54c8677b",
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      "url": "https://doi.org/10.1016/j.htct.2026.107951"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RC633-647.5",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "CYTOGENETIC AND GENOMIC ANALYSIS IN A CHILD WITH MYELODYSPLASTIC SYNDROME ASSOCIATED WITH HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS: CASE REPORT AND LITERATURE REVIEW",
  "title_text": "CYTOGENETIC AND GENOMIC ANALYSIS IN A CHILD WITH MYELODYSPLASTIC SYNDROME ASSOCIATED WITH HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS: CASE REPORT AND LITERATURE REVIEW",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:35Z",
  "url": "https://research.draconitic.com/paper/de5hx47qw0y9s",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}