First reports of primary ciliary dyskinesia caused by a shared DNAH11 allele in Canadian Inuit

Abstract

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.

Primary ciliary dyskinesia as a common cause of bronchiectasis in the Canadian Inuit population

“…1 An increased prevalence of non-CF bronchiectasis later in life has also been reported. 2 The reasons for this are not fully understood and are likely to be multifactorial, however the findings of Hunter-Schouela et al 3 in this issue of the journal may provide a missing link. They report a novel, pathogenic, possible founder DNA variant causing primary ciliary dyskinesia (PCD) in Inuit patients from different geographical areas of the Nunavut (Qikiqtaaluk region, Baffin Island) and Nunavik (Northern Qebec) regions in Canada, which may well be a contributing factor to the finding of increased bronchiectasis in this population.…”

Racial disparities in primary ciliary dyskinesia: Defining the problem and potential solutions

“…16 This is supported by recent reports of possible PCD founder variants in Native North American populations who are known for disproportionately high rates of suppurative respiratory disease yet remain woefully underinvestigated for potential etiologies. 18,19 Additionally, the suppurative respiratory symptoms associated with PCD in childhood are similar to cystic fibrosis (CF). 20 Although the CF population has become increasingly more diverse, CF is still much more prevalent in White people.…”