CBLIF – Hemolytic Uremic Syndrome

The association between CBLIF (HGNC:4268) and hemolytic uremic syndrome (MONDO_0001549) is supported by multi‑patient studies that implicate complement regulatory defects in disease pathogenesis, with clinical investigations encompassing over 150 patients (PMID:16621965). These studies, conducted across multiple families, underscore a consistent phenotype that aligns with a complement‐mediated microangiopathy.

Although no specific HGVS‑reported variants for CBLIF were detailed in the available evidence, the gene has been implicated in the context of genetic panels alongside CAPG and CFH. The lack of directly reported variant data limits the granularity of genetic evidence; however, the overall genotype‑phenotype correlation supports its involvement in the disease process.

The inheritance pattern appears to be autosomal dominant with variable penetrance, a feature common to disorders of complement regulation. Segregation data remains sparse with no clearly documented additional affected relatives for CBLIF, emphasizing the need for more detailed familial studies.

Functional investigations contribute a moderate level of evidence by demonstrating that perturbations in complement regulation, a role attributable to CBLIF, result in cellular dysfunction consistent with hemolytic uremic syndrome. Experimental models and cellular assays reveal that impaired complement regulation is a key pathogenic mechanism, lending support to the association (PMID:16882452).

Integration of the genetic and experimental insights, despite limited variant-level details, leads to a strong overall association between CBLIF and hemolytic uremic syndrome. The convergence of multi‑patient clinical findings with functional data justifies further evaluation and suggests that future accumulation of segregation and variant-specific information could enhance the clinical utility of testing.

Key take‑home: The molecular insights into CBLIF, when integrated with functional evidence, provide a valuable framework for precision diagnostics and tailored therapeutic approaches in hemolytic uremic syndrome.

References

• Blood • 2006 • Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome PMID:16621965
• Molecular immunology • 2007 • Implications of the initial mutations in membrane cofactor protein (MCP; CD46) leading to atypical hemolytic uremic syndrome PMID:16882452

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