Missense variants in KATNA1 alter microtubule dynamics and underlie dominant macular dystrophy.

Missense variants in KATNA1 (the catalytic p60 subunit of katanin) impairing microtubule severing; accumulation of acetylated microtubules in the cytoplasm and primary cilium.

This study identifies KATNA1, encoding the p60 subunit of katanin, as a previously unrecognised cause of autosomal dominant macular dystrophy. Ten heterozygous missense variants affecting six conserved amino acids were found in 21 individuals from 16 unrelated families worldwide, all with non-syndromic macular dystrophy of variable severity. Structural analyses and patient fibroblasts show impaired katanin assembly and accumulation of acetylated microtubules, with KATNA1 localising to photoreceptors. The authors estimate the gene could account for about 4 % of unresolved macular dystrophies.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A solid first-description study: 16 families, a coherent functional case (structure, fibroblasts, retinal localisation) and an original cytoskeletal mechanism for macular dystrophy. The target is already captured by WES/WGS — the challenge is annotating these missense variants, now made easier. One caveat: this is a preprint (Research Square), to be confirmed after peer review.

Analysis by Dr Thibaut Benquey