Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
Department of Medicine and Robarts Research Institute, Western University, London, Ontario, Canada.
Pediatr Pulmonol. 2023 Jul;58(7):1942-1949. doi: 10.1002/ppul.26414. Epub 2023 Apr 23.
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.
We report a case series of seven Inuit patients with PCD identified by genetic testing in three Canadian PCD centers.
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.
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.
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、频繁且严重的中耳炎、慢性鼻-鼻窦炎、新生儿呼吸窘迫和内脏器官侧位缺陷。虽然因纽特人中常见严重下呼吸道感染和支气管扩张症，但在该人群中尚未发现 PCD。
我们报告了三个加拿大 PCD 中心通过基因检测发现的 7 例 PCD 的因纽特患者病例系列。
患者年龄在 4 至 59 岁之间（在最后一次评估时），来自魁北克北部的努纳武特地区（巴芬岛，n=5）或努纳维克（n=2）。他们具有 PCD 的典型特征，包括新生儿呼吸窘迫（5 例）、全内脏反位（4 例）、支气管扩张症（4 例）、慢性肺不张（6 例）和慢性中耳炎（6 例）。大多数患者有慢性鼻炎。基因评估显示，所有患者在 NM_001277115.1：c.4095+2C>A 上均存在 DNAH11 的纯合致病性变异。
在努纳特（因纽特人居住地）的不同地区发现这种纯合 DNAH11 变异提示这是一种可能在因纽特人中广泛存在的创始突变。因此，PCD 可能是该人群慢性肺部、鼻窦和中耳疾病的重要原因。有慢性肺部疾病（包括支气管扩张症或侧位缺陷）的因纽特人应进行 PCD 的基因检测。在因纽特地区，应考虑将 PCD 基因分析纳入常规新生儿筛查。
