Home / Deep Research / CD16 Deficiency

CD16 Deficiency

CD16 Deficiency Deep Research Fallback

⚠️ Fallback MONDO:0014313

CD16 Deficiency Deep Research Fallback

Provider Attempts

No deep-research provider run was performed for this entry before the initial curation. That was a mistake, and it was causal rather than procedural: the two most important papers about this allele were missed, and both were reachable from the reference list of a paper already cached in the same PR. This record documents the literature sweep performed afterwards, in response to review.

Literature Scope

The entity is FCGR3A L66H homozygosity (MONDO:0014313, immunodeficiency 20). Four homozygotes are published. All four are now curated:

  • PMID:8608639 — Jawahar 1996, Clin Exp Immunol. Index patient. Reduced spontaneous cytotoxicity, intact ADCC, reduced circulating NK cells gated as CD56(+)CD3(-) without CD16.
  • PMID:8874200 — de Vries 1996, Blood. A second, independent homozygote, numbered p.L48H from the mature protein. Recurrent viral respiratory infection, severe course after BCG, EBV and VZV — but normal spontaneous cytotoxicity and normal ADCC on formal testing, and an explicit closing caveat asking whether the genotype is causally related to NK deficiency at all. Reachable from references_cache/PMID_23006327.md as reference 17.
  • PMID:23006327 — Grier 2012, J Clin Invest. Second affected patient plus the NK-92 reconstitution establishing the CD16-CD2 mechanism.
  • PMID:34448085 — Izadi 2021, J Clin Immunol. Asymptomatic homozygote found on newborn TREC screening, with normal NK lytic function and normal CD56-bright/CD56-dim distribution. Reports the gnomAD frequency (~5% overall, ~100 homozygotes) and concludes the variant is unlikely to be a direct genetic cause. Also documents the flow-cytometry gating artifact by which an L66H homozygote reads as NK-cytopenic under a CD16-inclusive gate.

What the sweep changed

The initial entry was built on two of the four homozygotes, and the two omitted were the two that argue hardest against a simple causal model. Incorporating them changed the entry substantively rather than cosmetically:

  • genetic.relationship_type moved from CAUSATIVE to DISPUTED.
  • The variant's clinical_significance moved from PATHOGENIC to UNCERTAIN_SIGNIFICANCE.
  • The Deficient Spontaneous NK Cell Cytotoxicity node gained two REFUTE-graded evidence items and a PROVISIONAL mechanism confidence.
  • A new l66h_pathogenicity_disputed CONTROVERSY was added, and the existing NK-count controversy was rewritten around three distinct mechanisms — gating artifact, genuinely low count in the index patient (whose gate did not include CD16, so the artifact does not explain it), and normal counts in two others.
  • prevalence now separates the rarity of the reported syndrome from the commonness of the genotype.

Searches run

PubMed, via the MCP PubMed server:

  • FCGR3A CD16 deficiency natural killer cell spontaneous cytotoxicity immunodeficiency
  • CD16 FCGR3A natural killer immunodeficiency herpesvirus
  • natural killer cell deficiency epitope-deficient Fc receptor type IIIA CD16
  • Grier CD16 spontaneous NK cell cytotoxicity human immunodeficiency-causing mutation
  • Reference-list traversal of references_cache/PMID_23006327.md (refs 16, 17)

GeneReviews: GeneReviews[TI] AND (FCGR3A OR "natural killer cell deficiency" OR "immunodeficiency 20") returns no chapter, so none is cited.