RPGR gene encodes retinitis pigmentosa guanosine triphosphatase regulator protein, mutations of which cause 70% of the X-linked retinitis pigmentosa (XLRP) cases. Rarely, RPGR mutations can also cause primary ciliary dyskinesia (PCD), a multisystem disorder characterized by recurrent respiratory tract infections, sinusitis, bronchiectasis, and male subfertility. Two patients with PCD_RP and their relatives were analyzed using DNA sequencing, transmission electron microscopy (TEM), immunofluorescence (IF), photometry, and high-speed videomicroscopy. The Polish patient carried a previously known c.154G>A substitution (p.Gly52Arg) in exon 2 (known to affect splicing); the mutation was co-segregating with the XLRP symptoms in his family. The c.824 G>T mutation (p. Gly275Val) in the Australian patient was a de novo mutation. In both patients, TEM and IF did not reveal any changes in the respiratory cilia structure. However, following ciliogenesis in vitro, in contrast to the ciliary beat frequency, the ciliary beat coordination in the spheroids from the Polish proband and his relatives carrying the c.154G>A mutation was reduced. Analysis of the ciliary alignment indicated severely disturbed orientation of cilia. Therefore, we confirm that defects in the RPGR protein may contribute to syndromic PCD. Lack of ultrastructural defects in respiratory cilia of the probands, the reduced ciliary orientation and the decreased coordination of the ciliary bundles observed in the Polish patient suggested that the RPGR protein may play a role in the establishment of the proper respiratory cilia orientation.
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