Data Scarcity
-
Fewer Studies: Notably limited research coverage compared to prevalent mutations like F508del.
-
Cohort Size Limitations: Sample sizes often statistically underpowered.
-
Mitigation: Use confidence-weighting to favor robust datasets (e.g., multi-center or meta-analyses); highlight provisional interpretations from small-N sources.
Diagnostic Gaps
-
Absent from Early Panels: Systematically excluded from pre-2005 genotyping platforms.
-
False Negatives: Diagnostic sensitivity compromised in historical screening.
-
Mitigation: Apply confidence decay to legacy diagnostic cohorts and flag potential under-detection zones.
Phenotypic Variability
-
Broader Outcome Range: Despite classification as Class I, pulmonary and digestive outcomes vary significantly.
-
Modifiers at Play: Influence from secondary genes (e.g., TGF-β1, MBL2) may account for unexpected phenotypic heterogeneity.
Regional Bias
-
Ethnic Concentration: Disproportionately observed in specific populations, notably Eastern Europe and Ashkenazi Jewish communities.
-
Mitigation: Explicit logging and visualization of data origin to contextualize prevalence and study generalizability.
Nomenclature Instability
-
Historical references include:
-
2184insA
-
c.2052dupA
-
p.Gln685ThrfsX4
-
-
Implications: Variability complicates literature searches and ontology linkage.