Bi-Allelic PRKCZ Loss-of-Function Variants and Adult-Onset Retinitis Pigmentosa

Are bi-allelic variants in PRKCZ associated with adult-onset autosomal recessive retinitis pigmentosa, and what is the underlying disease mechanism? In this collaborative case series study, bi-allelic loss-of-function variants of PRKCZ were identified in 13 individuals affected with adult-onset retinitis pigmentosa from 10 unrelated families of different ethnic backgrounds. All disease-associated variants disrupted the long retinal-enriched PRKCZ isoform containing the Phox and Bem1 (PB1) domain and were associated with impaired ciliogenesis and altered mitochondrial organization. These findings establish the association of PRKCZ loss of function with adult-onset, autosomal recessive retinitis pigmentosa through an isoform-specific disease mechanism, supporting consideration of PRKCZ in diagnostic gene panels.

Corresponding Author: Marco Tartaglia, PhD, Molecular Genetics and Functional Genomics Research Division, Bambino Gesù Children’s Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Viale di San Paolo 15, Rome, 00146 Italy (marco.tartaglia@opbg.net).

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