New paper out: Biallelic sequence and structural variants in RAX2 are a novel cause for autosomal recessive inherited retinal disease

Check out our new paper in Genetics in Medicine. You can read the abstract below, for the full text click here.

Purpose: RAX2 encodes a homeobox-containing transcription factor, in which four monoallelic pathogenic variants have been described in autosomal dominant conedominated retinal disease.
Methods: Exome sequencing in a European cohort with inherited retinal disease (IRD) (n=2086) was combined with protein structure modeling of RAX2 missense variants, bioinformatics analysis of deletion breakpoints, haplotyping of RAX2 variant c.335dup, and clinical assessment of biallelic RAX2-positive cases and carrier family members.
Results: Biallelic RAX2 sequence and structural variants were found in five unrelated European index cases, displaying non-syndromic autosomal recessive retinitis pigmentosa (ARRP) with an age of onset ranging from childhood to the mid 40s (average mid 30s). Protein structure modeling points to loss-of-function of the novel recessive missense variants and to a dominant-negative effect of the reported dominant RAX2 alleles. Structural variants were fine-mapped to disentangle their underlying mechanisms. Haplotyping of c.335dup in two cases suggests a common ancestry.
Conclusion: This study supports a role for RAX2 as novel disease gene for recessive IRD, broadening the mutation spectrum from sequence to structural variants and revealing a founder effect. The identification of biallelic RAX2 pathogenic variants in five unrelated families shows that RAX2 loss-of-function may be a non-negligible cause of IRD in unsolved ARRP cases.