RPGR mutations might cause reduced orientation of respiratory cilia
RPGR mutations might cause reduced orientation of respiratory cilia
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DOI：
10.1002/ppul.22632
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发表时间：
2013-04-01
影响因子：
3.1
通讯作者：
Witt, Michal
中科院分区：
文献类型：
--
作者：
Bukowy-Bieryllo, Zuzanna;Zietkiewicz, Ewa;Witt, Michal
RPGR基因编码色素性视网膜炎鸟苷三磷酸酶调节蛋白，其突变导致70%的x连锁色素性视网膜炎（XLRP）病例。罕见情况下，RPGR突变也可引起原发性纤毛运动障碍（PCD），这是一种以反复呼吸道感染、鼻窦炎、支气管扩张和男性生育能力低下为特征的多系统疾病。对2例PCD_RP患者及其亲属进行DNA测序、透射电子显微镜（TEM）、免疫荧光（IF）、光度法和高速视频显微镜分析。波兰患者在第2外显子携带先前已知的c.154G> a取代（p.Gly52Arg）（已知影响剪接）；突变与他家族的XLRP症状同时发生的c.824澳大利亚患者的g>t突变（p. Gly275Val）为新生突变。在两例患者中，TEM和IF未显示呼吸纤毛结构的任何变化。然而，在体外纤毛发生后，与纤毛搏动频率相反，波兰先证及其携带c.154G>A突变的亲属的球体中纤毛搏动协调性降低。纤毛对中分析显示纤毛取向严重紊乱。因此，我们确认RPGR蛋白的缺陷可能导致综合征性PCD。波兰患者呼吸纤毛超微结构缺陷缺失，纤毛取向降低，纤毛束协调性降低，提示RPGR蛋白可能在正确的呼吸纤毛取向的建立中发挥作用。儿科肺科杂志2013；48:352363。(c) 2012 Wiley期刊有限公司
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. Pediatr Pulmonol. 2013; 48:352363. (c) 2012 Wiley Periodicals, Inc.