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 l...

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Bibliographic Details
Published in:Pediatric Pulmonology
Main Authors: Hunter‐Schouela, Julia, Geraghty, Michael T., Hegele, Robert A., Dyment, David A., St Pierre, David, Richer, Julie, Sheffield, Holden, Zariwala, Maimoona A., Knowles, Michael R., Lehman, Anna, Dell, Sharon, Shapiro, Adam J., Kovesi, Thomas A.
Format: Article in Journal/Newspaper
Language:English
Published: Wiley 2023
Subjects:
Baffin Island
Baffin
inuit
Nunavut
Qikiqtaaluk
Nunavik
Online Access:http://dx.doi.org/10.1002/ppul.26414
https://onlinelibrary.wiley.com/doi/pdf/10.1002/ppul.26414
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Summary: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.

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