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

Autor: Baz-Redón N; Growth and Development Research Group, Vall d'Hebron Research Institute (VHIR), Hospital Universitari Vall d'Hebron, 08035 Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain., Sánchez-Bellver L; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain.; Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, 08028 Barcelona, Spain., Fernández-Cancio M; Growth and Development Research Group, Vall d'Hebron Research Institute (VHIR), Hospital Universitari Vall d'Hebron, 08035 Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain., Rovira-Amigo S; Growth and Development Research Group, Vall d'Hebron Research Institute (VHIR), Hospital Universitari Vall d'Hebron, 08035 Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain.; Department of Paediatrics, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain., Burgoyne T; Royal Brompton Hospital, Guy's and St Thomas' NHS Foundation Trust, London SW3 6NP, UK.; Institute of Ophthalmology, University College London, London EC1V 9EL, UK., Ranjit R; Royal Brompton Hospital, Guy's and St Thomas' NHS Foundation Trust, London SW3 6NP, UK., Aquino V; Plataforma Andaluza de Medicina Computacional, Fundación Pública Andaluza Progreso y Salud, 41092 Sevilla, Spain., Toro-Barrios N; Plataforma Andaluza de Medicina Computacional, Fundación Pública Andaluza Progreso y Salud, 41092 Sevilla, Spain., Carmona R; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain.; Plataforma Andaluza de Medicina Computacional, Fundación Pública Andaluza Progreso y Salud, 41092 Sevilla, Spain., Polverino E; Pneumology Research Group, Vall d'Hebron Research Institute (VHIR), Hospital Universitari Vall d'Hebron, 08035 Barcelona, Spain.; Pneumology Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain., Cols M; Paediatric Pulmonology Department and Cystic Fibrosis Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain., Moreno-Galdó A; Growth and Development Research Group, Vall d'Hebron Research Institute (VHIR), Hospital Universitari Vall d'Hebron, 08035 Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain.; Department of Paediatrics, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain.; Department of Paediatrics, Obstetrics, Gynecology, Preventive Medicine and Public Health, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain., Camats-Tarruella N; Growth and Development Research Group, Vall d'Hebron Research Institute (VHIR), Hospital Universitari Vall d'Hebron, 08035 Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain., Marfany G; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain.; Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, 08028 Barcelona, Spain.; Institute of Biomedicine (IBUB-IRSJD), Universitat de Barcelona, 08028 Barcelona, Spain.
Jazyk: angličtina
Zdroj: Cells [Cells] 2024 Mar 16; Vol. 13 (6). Date of Electronic Publication: 2024 Mar 16.
DOI: 10.3390/cells13060524
Abstrakt: 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.
Databáze: MEDLINE
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