Computational Evidence for Digenic Contribution of <i>AIPL1</i> and <i>BBS2</i> Rare Variants in Inherited Retinal Dystrophy.

ABSTRACT: Inherited retinal dystrophies (IRDs) are clinically and genetically heterogeneous disorders. Most IRDs follow a monogenic inheritance pattern. However, an increasing number of unresolved cases suggest the possible contribution of oligogenic or digenic mechanisms. Here, we report two ultra-rare missense variants-AIPL1 R302L and BBS2 P134R-that co-segregate with early-onset nonsyndromic retinal degeneration in affected individuals from a non-consanguineous family. We performed a multi-level computational investigation to assess whether these variants may act through a convergent pathogenic mechanism. Using AlphaFold2-predicted structures, we modeled both wild-type and mutant proteins, introduced point mutations, and performed energy minimization and validation. FoldX, DynaMut2, and DUET all

SUBMITTER: Alibrandi S 

PROVIDER: S-EPMC12524372 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature