Functional studies in a neonate with a DOCK11 VUS guide clinical care

Area of Science:

• Genomic medicine
• Immunology
• Clinical diagnostics

Background:

• Genetic variants of uncertain significance (VUS) pose diagnostic challenges.
• Functional studies are crucial for interpreting VUS in rare diseases.
• Negative findings from functional studies are often underreported.

Purpose of the Study:

• To illustrate how negative functional study results can guide clinical management.
• To emphasize the importance of publishing instructive negative findings.
• To showcase the utility of functional genomics in neonatology.

Main Methods:

• Case report of a neonate with a DOCK11 variant of uncertain significance.
• Application of functional studies to assess the pathogenicity of the DOCK11 variant.
• Clinical correlation of functional study results with patient phenotype.

Main Results:

• Negative functional studies provided definitive evidence against pathogenicity of the DOCK11 variant.
• This guided the clinical care decisions for the neonate.
• The findings underscore the utility of negative results in variant interpretation.

Conclusions:

• Negative functional studies can meaningfully guide clinical care, even in complex cases.
• Publishing negative findings is essential for advancing immunology and genomic medicine.
• This case highlights the broader impact of reporting instructive negative results.