PDF(Pubmed)
Abstract：
UNASSIGNED: The mutations in the RPGR (retinitis pigmentosa GTPase regulator) gene are the most common cause of X-linked retinitis pigmentosa (XLRP), a rare genetic disorder affecting the photoreceptor cells in the retina. Several reported cases identified this gene as a genetic link between retinitis pigmentosa (RP) and primary ciliary dyskinesia (PCD), characterised by impaired ciliary function predominantly in the respiratory tract. Since different mutations in the same gene can result in various clinical manifestations, it is important to describe a correlation between the gene variant and the observed phenotype.
UNASSIGNED: Two young brothers from a non-consanguineous Slovak family with diagnosed retinal dystrophy and recurrent respiratory infections were examined. Suspected PCD was diagnosed based on a PICADAR questionnaire, nasal nitric oxide analysis, transmission electron microscopy, high-speed video microscopy analysis, and genetic testing.
UNASSIGNED: We identified a novel frameshift RPGR mutation NM_001034853: c.309_310insA, p.Glu104Argfs*12, resulting in a complex X-linked phenotype combining PCD and RP. In our patients, this mutation was associated with normal ultrastructure of respiratory cilia, reduced ciliary epithelium, more aciliary respiratory epithelium, shorter cilia, and uncoordinated beating with a frequency at a lower limit of normal beating, explaining the clinical manifestation of PCD in our patients.
UNASSIGNED: The identified novel pathogenic mutation in the RPGR gene expands the spectrum of genetic variants associated with the X-linked PCD phenotype overlapping with RP, highlighting the diversity of mutations contributing to the disorder. The described genotype-phenotype correlation can be useful in clinical practice to recognise a broader spectrum of PCD phenotypes as well as for future research focused on the genetic basis of PCD, gene interactions, the pathways implicated in PCD pathogenesis, and the role of RPGR protein for the proper functioning of cilia in various tissues throughout the body.
UNASSIGNED: Two young brothers from a non-consanguineous Slovak family with diagnosed retinal dystrophy and recurrent respiratory infections were examined. Suspected PCD was diagnosed based on a PICADAR questionnaire, nasal nitric oxide analysis, transmission electron microscopy, high-speed video microscopy analysis, and genetic testing.
UNASSIGNED: We identified a novel frameshift RPGR mutation NM_001034853: c.309_310insA, p.Glu104Argfs*12, resulting in a complex X-linked phenotype combining PCD and RP. In our patients, this mutation was associated with normal ultrastructure of respiratory cilia, reduced ciliary epithelium, more aciliary respiratory epithelium, shorter cilia, and uncoordinated beating with a frequency at a lower limit of normal beating, explaining the clinical manifestation of PCD in our patients.
UNASSIGNED: The identified novel pathogenic mutation in the RPGR gene expands the spectrum of genetic variants associated with the X-linked PCD phenotype overlapping with RP, highlighting the diversity of mutations contributing to the disorder. The described genotype-phenotype correlation can be useful in clinical practice to recognise a broader spectrum of PCD phenotypes as well as for future research focused on the genetic basis of PCD, gene interactions, the pathways implicated in PCD pathogenesis, and the role of RPGR protein for the proper functioning of cilia in various tissues throughout the body.
摘要：
■RPGR（色素性视网膜炎GTP酶调节因子）基因的突变是X连锁色素性视网膜炎（XLRP）的最常见原因，一种影响视网膜感光细胞的罕见遗传病。一些报道的病例将该基因鉴定为色素性视网膜炎（RP）和原发性纤毛运动障碍（PCD）之间的遗传联系，主要表现为呼吸道纤毛功能受损。由于同一基因的不同突变会导致各种临床表现，描述基因变异与观察到的表型之间的相关性是很重要的。
■检查了两名来自斯洛伐克非近亲家庭的年轻兄弟，他们被诊断为视网膜营养不良和反复呼吸道感染。可疑PCD是根据PICADAR问卷诊断的，鼻腔一氧化氮分析，透射电子显微镜,高速视频显微镜分析，和基因检测。
■我们鉴定了一个新的移码RPGR突变NM_001034853：c.309_310insA，p.Glu104Argfs*12，导致结合PCD和RP的复杂X连锁表型。在我们的病人中，这种突变与呼吸道纤毛的正常超微结构有关，睫状上皮减少，更多的纤毛呼吸上皮，较短的纤毛，和不协调的跳动，频率在正常跳动的下限，解释我们患者PCD的临床表现。
■在RPGR基因中发现的新的致病突变扩展了与与RP重叠的X连锁PCD表型相关的遗传变异谱，突出了导致这种疾病的突变的多样性。所描述的基因型-表型相关性可用于临床实践，以识别更广泛的PCD表型，以及未来的研究集中在PCD的遗传基础，基因相互作用，与PCD发病机制有关的途径，以及RPGR蛋白对整个身体各种组织中纤毛的正常功能的作用。
■检查了两名来自斯洛伐克非近亲家庭的年轻兄弟，他们被诊断为视网膜营养不良和反复呼吸道感染。可疑PCD是根据PICADAR问卷诊断的，鼻腔一氧化氮分析，透射电子显微镜,高速视频显微镜分析，和基因检测。
■我们鉴定了一个新的移码RPGR突变NM_001034853：c.309_310insA，p.Glu104Argfs*12，导致结合PCD和RP的复杂X连锁表型。在我们的病人中，这种突变与呼吸道纤毛的正常超微结构有关，睫状上皮减少，更多的纤毛呼吸上皮，较短的纤毛，和不协调的跳动，频率在正常跳动的下限，解释我们患者PCD的临床表现。
■在RPGR基因中发现的新的致病突变扩展了与与RP重叠的X连锁PCD表型相关的遗传变异谱，突出了导致这种疾病的突变的多样性。所描述的基因型-表型相关性可用于临床实践，以识别更广泛的PCD表型，以及未来的研究集中在PCD的遗传基础，基因相互作用，与PCD发病机制有关的途径，以及RPGR蛋白对整个身体各种组织中纤毛的正常功能的作用。
