TBC1D32: A newcomer to the list of genes responsible for retinitis pigmentosa with a role in retinal ciliogenesis.

In a study published in The Journal of clinical Investgation, Muriel Perron’s team at the Paris-Saclay Institute of Neuroscience (NeuroPSI), in collaboration with teams from the Montpellier Neuroscience Institute (INM), has identified TBC1D32 as a causative gene for retinitis pigmentosa, a genetic degenerative disease of the retina leading to vision loss.
Currently, the genetic origins remain undetermined in around 40% of individuals affected by retinitis pigmentosa. In this study, we report 4 patients presenting with this condition from 3 unrelated families with variants in TBC1D32. To validate TBC1D32 as a putative retinitis pigmentosa causative gene, in vivo approaches using Xenopus and retinal models derived from iPSCs were employed. This research led to the identification of a central role for TBC1D32 in the ciliogenesis of retinal pigment epithelium cells, as well as in the process of photoreceptor differentiation. Overall, our data highlight a critical role for TBC1D32 in retinal development and demonstrate that TBC1D32 mutations lead to retinitis pigmentosa. This work has implications for alleviating current diagnostic deadlocks and supports the recommendation to include TBC1D32 in the list of candidate genes to be screened for both isolated and syndromic retinitis pigmentosa.

TBC1D32 variants disrupt retinal ciliogenesis and cause retinitis pigmentosa. Béatrice Bocquet, Caroline Borday, Nejla Erkilic, Daria Mamaeva, Alicia Donval, Christel Masson, Karine Parain, Karolina Kaminska, Mathieu Quinodoz, Irene Perea-Romero, Gema Garcia-Garcia, Carla Jimenez-Medina, Hassan Boukhaddaoui, Arthur Coget, Nicolas Leboucq, Giacomo Calzetti, Stefano Gandolfi, Antonio Percesepe, Valeria Barili, Vera Uliana, Marco Delsante, Francesca Bozzetti, Hendrik P.N. Scholl, Marta Corton, Carmen Ayuso, Jose M. Millan, Carlo Rivolta, Isabelle Meunier, Muriel Perron, and Vasiliki Kalatzis.

Article published in JCI Insight - Access to the manuscript