Primary Ciliary Dyskinesia and Retinitis Pigmentosa: Novel Variant and Possible Modifier Gene.

TitlePrimary Ciliary Dyskinesia and Retinitis Pigmentosa: Novel Variant and Possible Modifier Gene.
Publication TypeJournal Article
Year of Publication2024
AuthorsBaz-Redón, N, Sánchez-Bellver, L, Fernández-Cancio, M, Rovira-Amigo, S, Burgoyne, T, Ranjit, R, Aquino, V, Toro-Barrios, N, Carmona, R, Polverino, E, Cols, M, Moreno-Galdó, A, Camats-Tarruella, N, Marfany, G
Date Published2024 Mar 16
KeywordsCiliary Motility Disorders; Eye Proteins; Genes, Modifier; Humans; Male; mutation; Retinitis pigmentosa

We report a novel missense variant co-segregated with a familial X-linked retinitis pigmentosa (XLRP) case. The brothers were hemizygous for this variant, but only the proband presented with primary ciliary dyskinesia (PCD). Thus, we aimed to elucidate the role of the variant and other modifier genes in the phenotypic variability observed in the family and its impact on motile cilia. The pathogenicity of the variant on the RPGR protein was evaluated by in vitro studies transiently transfecting the mutated gene, and immunofluorescence analysis on nasal brushing samples. Whole-exome sequencing was conducted to identify potential modifier variants. In vitro studies showed that the mutated RPGR protein could not localise to the cilium and impaired cilium formation. Accordingly, RPGR was abnormally distributed in the siblings' nasal brushing samples. In addition, a missense variant in was identified. The concurrent variant influenced ciliary mislocalisation of the protein. We provide a comprehensive characterisation of motile cilia in this XLRP family, with only the proband presenting PCD symptoms. The variant's pathogenicity was confirmed, although it alone does not explain the respiratory symptoms. Finally, the gene may be a potential modifier for respiratory symptoms in patients with mutations.

Alternate JournalCells
PubMed ID38534367
PubMed Central IDPMC10968961
Grant ListACCI 2021 / / Centre for Biomedical Network Research on Rare Diseases /
2022FI_B2 00108 / / Government of Catalonia /
2021SGR-01093 / / Government of Catalonia /
PID2022-140957OB-I00 / / Ministerio de Ciencia e Innovación /
PI20/01419 / / Instituto de Salud Carlos III /