'No causative variants found': an unusual presentation of PAX2-related disorder not detected on rapid whole exome...

Paired box 2 (PAX2)-related disorder, also known as renal coloboma syndrome, is a variably penetrant autosomal dominant condition, associated with renal and ophthalmological abnormalities. We report a child with PAX2-related disorder who presented atypically with acute ataxia on a background of stage 3 chronic kidney disease. Extensive biochemical, radiological and gene agnostic rapid trio exome sequencing was non-diagnostic. Identification of bilateral optic disc colobomas in the proband and his father raised the suspicion of an inherited PAX2-related disorder. No causative variants were identified on a focused review of the filtered genomic data. Given the strong suspicion of an inherited monogenic disorder, whole genome trio sequencing was requested. Analysis assuming incomplete penetrance identified a paternally inherited PAX2 microdeletion encompassing exon 4. This case adds to evidence of a broader PAX2-associated phenotype. It highlights the importance of a clinical genetics and mainstream interface when navigating and interpreting genetic testing.