Whole-exome sequencing identification of novel DNAH5 mutations in a young patient with primary ciliary dyskinesia.
Whole-exome sequencing identification of novel DNAH5 mutations in a young patient with primary ciliary dyskinesia.
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DOI：
10.3892/mmr.2016.5871
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发表时间：
2016-12
影响因子：
3.4
通讯作者：
Fujisawa T
中科院分区：
文献类型：
--
作者：
Kano G;Tsujii H;Takeuchi K;Nakatani K;Ikejiri M;Ogawa S;Kubo H;Nagao M;Fujisawa T
原发性纤毛运动障碍(PCD)是一种罕见的遗传性疾病，由全身纤毛结构和/或功能损害引起。PCD的早期诊断对于预防长期后遗症很重要，但由于PCD的表型异质性，早期诊断是一项挑战。在目前的研究中，在几次努力控制顽固性呼吸道症状后，这名患者在9岁时被诊断为PCD。患者从儿童早期就开始出现慢性咳嗽，并有多次肺炎、中耳炎和渗出性鼻窦炎。未见内翻或其他异位的报道。连续胸部X光片显示右中叶持续肺不张和支气管扩张。在患者9岁时，对其纤毛进行了电子显微镜检查和遗传分析。鼻粘膜活检标本的电子显微镜显示外动力蛋白臂丢失。基因组全外显子分析显示，36号外显子的DNAH5：NM_001369.2：C.5983C>；T，p.Arg1995X和54号外显子的NM_001369.2：C.9101delG，p.Gly3034ValfsX22存在复合杂合性突变，这两种突变均未见文献报道。值得注意的是，据我们所知，这是第一例报告的由DNAH5突变引起的日本患者PCD病例。
Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by structural and/or functional impairment of cilia throughout the whole body. Early diagnosis of PCD is important for the prevention of long-term sequelae, however early diagnosis is a challenge due to the phenotypic heterogeneity of PCD. In the current study, the patient with PCD was diagnosed at nine years old following several efforts to control intractable airway symptoms. The patient experienced a chronic productive cough beginning in early childhood and had multiple episodes of pneumonia and otitis media with effusion and sinusitis. No situs inversus or other heterotaxias were reported. Serial chest X-rays exhibited persistent atelectasis and bronchiectasis in the right middle lobe. When the patient was nine years old, electron microscopy of his cilia and genetic analysis were conducted. Electron microscopy of a biopsy specimen from the nasal mucosa indicated loss of the outer dynein arms. Whole-exome analysis of the genome demonstrated the presence of compound heterozygous mutations in DNAH5: NM_001369.2:c.5983C>T, p.Arg1995X in exon 36 and NM_001369.2:c.9101delG, p.Gly3034ValfsX22 in exon 54; neither of which have been previously reported in the literature in a Japanese patient. Notably, this case is, to the best of our knowledge, the first reported case of PCD caused by the DNAH5 mutation in a Japanese patient.