02536nas a2200373   4500008004100000022001400041245010000055210006900155260001600224490000700240520133200247653003101579653001701610653002001627653001101647653000901658653001301667653002501680100002301705700002801728700003101756700002501787700002101812700001601833700002101849700002501870700002101895700001901916700001601935700002701951700002901978700001902007856013602026       2024                        eng d  a2073-440900aPrimary Ciliary Dyskinesia and Retinitis Pigmentosa: Novel  Variant and Possible Modifier Gene.0 aPrimary Ciliary Dyskinesia and Retinitis Pigmentosa Novel Varian  c2024 Mar 160 v133 a<p>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.</p>10aCiliary Motility Disorders10aEye Proteins10aGenes, Modifier10aHumans10aMale10amutation10aRetinitis pigmentosa1 aBaz-Redón, Noelia1 aSánchez-Bellver, Laura1 aFernández-Cancio, Mónica1 aRovira-Amigo, Sandra1 aBurgoyne, Thomas1 aRanjit, Rai1 aAquino, Virginia1 aToro-Barrios, Noemí1 aCarmona, Rosario1 aPolverino, Eva1 aCols, Maria1 aMoreno-Galdó, Antonio1 aCamats-Tarruella, Núria1 aMarfany, Gemma  uhttps://www.clinbioinfosspa.es/content/primary-ciliary-dyskinesia-and-retinitis-pigmentosa-novel-variant-and-possible-modifier-gene