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

Authors :
Noelia Baz-Redón
Laura Sánchez-Bellver
Mónica Fernández-Cancio
Sandra Rovira-Amigo
Thomas Burgoyne
Rai Ranjit
Virginia Aquino
Noemí Toro-Barrios
Rosario Carmona
Eva Polverino
Maria Cols
Antonio Moreno-Galdó
Núria Camats-Tarruella
Gemma Marfany
Source :
Cells, Vol 13, Iss 6, p 524 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

We report a novel RPGR 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 RPGR 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 RPGR 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 CEP290 was identified. The concurrent RPGR 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 CEP290 gene may be a potential modifier for respiratory symptoms in patients with RPGR mutations.

Details

Language :
English
ISSN :
20734409
Volume :
13
Issue :
6
Database :
Directory of Open Access Journals
Journal :
Cells
Publication Type :
Academic Journal
Accession number :
edsdoj.b269912dace343959872be6b3a0e8664
Document Type :
article
Full Text :
https://doi.org/10.3390/cells13060524