Bone Marrow Failure IEIs (IUIS Table 9)

name: Bone Marrow Failure IEIs
display_name: Bone Marrow Failure IEIs (IUIS Table 9)
creation_date: "2026-08-20T00:00:00Z"
description: >-
  IUIS Table 9 — bone marrow failure. These inborn errors of immunity reach the
  immune system from below, through failure of the haematopoietic stem and
  progenitor compartment itself rather than through a lesion in a mature immune
  cell or pathway. The underlying defects are typically in genome maintenance,
  DNA replication or telomere biology, so the immunodeficiency arrives packaged
  with cytopenias, growth failure, chromosomal instability and a substantial
  risk of myelodysplasia and malignancy.
grouping_basis:
- SHARED_MECHANISM
- SHARED_PHENOTYPE
grouping_rationale: >-
  Grouped on the IUIS Table 9 pattern: immunodeficiency as a consequence of
  haematopoietic failure. The table exists because these disorders are not
  immune-pathway diseases at all — the same genome-maintenance lesion that
  depletes lymphocytes also depletes the other lineages and drives
  cancer predisposition, which changes both the surveillance a patient needs and
  the calculus around haematopoietic stem cell transplantation. Members are kept
  as separate Disease entries because the specific genome-maintenance defect
  differs. No MONDO mapping: MONDO:0000159 (bone marrow failure syndrome) is a
  phenotype-defined class that does not subsume the listed member — verified
  2026-08-20 with `runoak -i sqlite:obo:mondo descendants -p i MONDO:0000159`,
  which does not return MONDO:0013118 — so mapping to it would assert a
  subsumption the ontology does not carry.
membership_criteria:
- description: >-
    A disorder belongs to IUIS Table 9 if it is an inborn error of immunity in
    which the immune defect arises from failure of the haematopoietic stem and
    progenitor compartment, typically through a genome-maintenance,
    DNA-replication or telomere-biology lesion.
  criteria_semantics: NECESSARY
  logic:
    criterion_predicate: HAS_CLASSIFICATION
    classification: "iuis_category:bone marrow failure"
    description: >-
      Assigned to IUIS Table 9 (bone marrow failure) via
      classifications.iuis_category on the member Disease entry. Stated in the
      keyed `<slot>:<value>` form so the audit reads the structured
      classifications block.
members:
- member: Nijmegen Breakage Syndrome-like Disorder
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Biallelic hypomorphic RAD50 variants destabilise the MRE11-RAD50-NBN
      double-strand-break sensor, abolishing damage-induced MRN focus formation
      and impairing ATM activation. The result is checkpoint failure,
      radioresistant DNA synthesis and chromosomal instability, clinically
      phenocopying Nijmegen breakage syndrome. RAD50 is one of the three
      entities newly added to Table 9 in the IUIS 2024 update, and its
      placement there rather than in the syndromic combined-immunodeficiency
      table (where NBS itself sits) is the distinction this grouping turns on.
    gene:
      preferred_term: RAD50
      term:
        id: hgnc:9816
        label: RAD50
notes: >-
  Created 2026-08-20 to give the IUIS Table 9 disorders a place in the Inborn
  Errors of Immunity tree; the member already carried
  `classifications.iuis_category: bone marrow failure` but was unreachable from
  the umbrella grouping. Intentionally unmapped to MONDO — see
  grouping_rationale. Single-member for now; the classical Table 9 entities
  (Fanconi anaemia, dyskeratosis congenita, Shwachman-Diamond syndrome,
  severe congenital neutropenia with marrow failure) are candidates as they are
  curated or assigned an iuis_category.