schema: eds-research/corpus/v1
category:
  id: genetics
  label: Genetics and biomarkers
  description: The molecular map — confirmed genes for twelve subtypes, the hEDS search, registries and cohorts.
  order: 30
records:
  - id: gen-heds-no-confirmed-gene
    kind: finding
    title: hEDS is the only subtype without a confirmed molecular basis
    summary: All twelve other 2017 subtypes have defined causative genes. For hEDS — the most common type — no confirmed molecular basis existed through 2024, forcing purely clinical diagnosis and the strict 2017 criteria as the only gate.
    subtypes: [heds]
    status: established
    criteria_era: international-2017
    evidence:
      - stratum: clinical
        tier: consensus-statement
        source_ids: [source-36ad1cab53c4cea4f4b4]
      - stratum: clinical
        tier: expert-review
        source_ids: [source-1ad3f0edd57e0fab1524]
    reviewed_at: "2026-09-16"
    tags: [genetics]
  - id: gen-klk15-first-candidate
    kind: finding
    title: KLK15 is the first gene associated with hEDS
    summary: Norris Lab whole-exome sequencing of 200 hEDS patients found rare variants across 14 of 15 kallikrein genes, with a recurrent KLK15 p.Gly226Asp variant segregating in multiple families; a knock-in mouse recapitulated tendon and cardiac-valve features. The authors and the society both caution this does not yet change diagnosis — it is the first candidate, not a test.
    date: "2025-08"
    date_precision: month
    subtypes: [heds]
    status: emerging
    criteria_era: international-2017
    evidence:
      - stratum: clinical
        tier: mechanistic-study
        source_ids: [source-ee867f99ac8808a4ef80]
      - stratum: gray
        tier: preprint
        source_ids: [source-daaa8e28125b9b3bb775]
      - stratum: community
        tier: patient-org-synthesis
        source_ids: [source-bb268c000069896e8023]
    corroboration: convergent
    reviewed_at: "2026-09-16"
    reassess_by: "2026-12-16"
    people: [Russell Norris]
    organizations: [Medical University of South Carolina]
    tags: [genetics, frontier]
  - id: gen-hedge-study
    kind: program
    title: HEDGE — the 1,000-participant hEDS genetic evaluation
    summary: The Hypermobile Ehlers-Danlos Genetic Evaluation study is the largest dedicated hEDS genetics effort, run under The Ehlers-Danlos Society's research program. First publications were expected late 2025 into 2026; this index tracks it as the pivotal watch item for the subtype.
    subtypes: [heds, hsd]
    status: emerging
    criteria_era: international-2017
    evidence:
      - stratum: registry
        tier: registry-report
        source_ids: [source-3440a2b9d5d99c580d3a]
      - stratum: community
        tier: patient-org-synthesis
        source_ids: [source-bb268c000069896e8023]
    corroboration: convergent
    reviewed_at: "2026-09-16"
    reassess_by: "2026-12-16"
    organizations: [The Ehlers-Danlos Society]
    tags: [genetics, registry, frontier]
  - id: gen-collagen-and-pathway-map
    kind: finding
    title: The molecular map concentrates in collagen and collagen-processing pathways
    summary: Confirmed subtype genes cluster into collagen structure (COL5A1/A2, COL3A1, COL1A1/A2, COL12A1), collagen processing (ADAMTS2, PLOD1), proteoglycan and glycosaminoglycan pathways (B4GALT7, B3GALT6, CHST14, DSE), complement (C1R, C1S), and signaling (TNXB, SLC39A13, ZNF469, PRDM5, FKBP14). The 2017 classification groups subtypes by shared pathway for research purposes.
    subtypes: [all-eds]
    status: established
    criteria_era: international-2017
    evidence:
      - stratum: clinical
        tier: consensus-statement
        source_ids: [source-36ad1cab53c4cea4f4b4]
      - stratum: clinical
        tier: expert-review
        source_ids: [source-be972ed50decef4cbf0b]
    reviewed_at: "2026-09-16"
    tags: [genetics]