简介:原发性纤毛运动障碍(PCD)是一种罕见的异质性疾病,由活动纤毛异常引起。在这个案例报告中,我们首先根据临床和放射学结果分析了一名怀疑患有PCD的先证者的临床和遗传数据.方法:进行全外显子组测序,并且在先证者中鉴定出RSPH4A基因的变体。Sanger测序用于验证先证者中的RSPH4A变体,她的妹妹,她的女儿和她的父母。最后,分析了患者的表型特征,为了更好地了解PCD中与听力损失相关的基因变异和PCD中RSPH4A变异的临床表现,对目前的文献进行了综述。结果:本先证者的主要临床症状包括逐渐混合性听力损失,中耳炎,嗅觉缺失,鼻窦炎,反复咳嗽和不孕症。根据基因测试结果,她的DNA测序揭示了RSPH4A外显子3内1321位的新的纯合T到C转换。以前从未报道过这种变体。纯合变体导致在441位精氨酸对色氨酸的氨基酸取代(p。Trp441Arg)。在先证者的姐姐身上也发现了同样的变体,在直系亲属中发现了一种杂合致病变异,包括先证者的女儿和父母.讨论:文献综述显示,已报道了RSPH4A中的16种致病变体。仅在RSPH4A(c.9213_6delAAGT)剪接位点突变的患者中观察到听力损失,和听力损失的具体类型没有描述。
Introduction: Primary ciliary dyskinesia (PCD) is a rare heterogeneous disease caused by abnormalities in motile cilia. In this case report, we first analyzed the clinical and genetic data of a proband who was suspected of having PCD on the basis of her clinical and radiological findings. Methods: Whole-exome sequencing was performed, and a variant in the
RSPH4A gene was identified in the proband. Sanger sequencing was used for validation of
RSPH4A variants in the proband, her sister, her daughter and her parents. Finally, the phenotypic features of the patient were analyzed, and the current literature was reviewed to better understand the gene variants in PCD related to hearing loss and the clinical manifestations of the
RSPH4A variant in PCD. Results: The chief clinical symptoms of this proband included gradual mixed hearing loss, otitis media, anosmia, sinusitis, recurrent cough and infertility. Her DNA sequencing revealed a novel homozygous T to C transition at position 1321 within exon 3 of RSPH4A according to genetic testing results. This variant had never been reported before. The homozygous variant resulted in an amino acid substitution of tryptophan by arginine at position 441 (p.Trp441Arg). The same variant was also found in the proband\'s sister, and a heterozygous pathogenic variant was identified among immediate family members, including the proband\'s daughter and parents. Discussion: A literature review showed that 16 pathogenic variants in
RSPH4A have been reported. Hearing loss had only been observed in patients with the
RSPH4A (c.921+3_6delAAGT) splice site mutation, and the specific type of hearing loss was not described.