Primary Ciliary Dyskinesia and Retinitis Pigmentosa : Novel RPGR Variant and Possible Modifier Gene
Baz-Redón, Noelia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Sánchez-Bellver, Laura (Universitat de Barcelona. Departament de Genètica, Microbiologia i Estadística)
Fernández Cancio, Mónica (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rovira-Amigo, Sandra (Hospital Universitari Vall d'Hebron)
Burgoyne, Thomas (Institute of Ophthalmology, University College London)
Ranjit, Rai (Royal Brompton Hospital (Londres, Regne Unit))
Aquino, Virginia (Fundación Pública Andaluza Progreso y Salud (Sevilla, Andalusia))
Toro-Barrios, Noemí (Fundación Pública Andaluza Progreso y Salud (Sevilla, Andalusia))
Carmona, Rosario (Fundación Pública Andaluza Progreso y Salud (Sevilla, Andalusia))
Polverino, Eva (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Cols, Maria (Hospital Sant Joan de Déu (Barcelona, Catalunya))
Moreno Galdó, Antonio (Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i de Medicina Preventiva i Salut Pública)
Camats Tarruella, Núria (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Marfany, Gemma (Universitat de Barcelona. Departament de Genètica, Microbiologia i Estadística)

Data:	2024
Resum:	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.
Ajuts:	Generalitat de Catalunya 2022FI_B2 00108 Generalitat de Catalunya 2021SGR-01093 Agencia Estatal de Investigación PID2022-140957OB-I00 Instituto de Salud Carlos III PI20/01419
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Primary cilia ; Motile cilia ; Primary ciliary dyskinesia ; Retinitis pigmentosa ; PCD ; XLRP ; RPGR ; CEP290 ; Modifier gene
Publicat a:	Cells, Vol. 13 (march 2024) , ISSN 2073-4409

DOI: 10.3390/cells13060524
PMID: 38534367

15 p, 10.6 MB

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