背景:原发性纤毛运动障碍(PCD)通常是一种常染色体隐性疾病,其特征是下呼吸道反复感染,频繁和严重的中耳炎,慢性鼻-鼻窦炎,新生儿呼吸窘迫,和器官侧向缺陷。严重的下呼吸道感染和支气管扩张在因纽特人很常见,PCD尚未在该人群中得到认可。
方法:我们报告了在加拿大三个PCD中心通过基因检测确定的7例因纽特人PCD患者。
结果:患者的年龄范围为4至59岁(在上次评估时),起源于Qikiqtaaluk地区(Baffin岛,n=5),努纳武特,或努纳维克(魁北克北部,n=2),加拿大。它们具有PCD的典型特征,包括新生儿呼吸窘迫(5例),全坐位倒置(四名患者),支气管扩张(四名患者),慢性肺不张(6例),和慢性中耳炎(6例)。大多数患有慢性鼻炎。遗传评估表明,在NM_001277115.1:c.40952C>A。
结论:在Nunangat(因纽特人家乡)的广泛不同部分中发现了这种纯合DNAH11变体,这表明这是一种可能在因纽特人中普遍存在的创始人突变。因此,PCD可能是慢性肺的重要病因,鼻窦,和中耳疾病在这个人群中。因纽特人患有慢性肺病,包括支气管扩张或侧向缺陷,应进行PCD基因检测。在因纽特人地区,应考虑在常规新生儿筛查中包括PCD遗传分析。
BACKGROUND: Primary ciliary dyskinesia (PCD) is typically an autosomal recessive disease characterized by recurrent infections of the lower respiratory tract, frequent and severe otitis media, chronic rhinosinusitis, neonatal respiratory distress, and organ laterality defects. While severe lower respiratory tract infections and bronchiectasis are common in Inuit, PCD has not been recognized in this population.
METHODS: We report a
case series of seven Inuit patients with PCD identified by genetic testing in three Canadian PCD centers.
RESULTS: Patients ranged from 4 to 59 years of age (at time of last evaluation) and originated in the Qikiqtaaluk region (Baffin Island, n = 5), Nunavut, or Nunavik (northern Quebec, n = 2), Canada. They had typical features of PCD, including neonatal respiratory distress (five patients), situs inversus totalis (four patients), bronchiectasis (four patients), chronic atelectasis (six patients), and chronic otitis media (six patients). Most had chronic rhinitis. Genetic evaluation demonstrated that all had homozygous pathogenic variants in DNAH11 at NM_001277115.1:c.4095+2C>A.
CONCLUSIONS: The discovery of this homozygous DNAH11 variant in widely disparate parts of the Nunangat (Inuit homelands) suggests this is a founder mutation that may be widespread in Inuit. Thus, PCD may be an important cause of chronic lung, sinus, and middle ear disease in this population. Inuit with chronic lung disease, including bronchiectasis or laterality defects, should undergo genetic testing for PCD. Consideration of including PCD genetic analysis in routine newborn screening should be considered in Inuit regions.