Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice / 医学前沿
Frontiers of Medicine
; (4): 957-971, 2023.
Article
en En
| WPRIM
| ID: wpr-1010803
Biblioteca responsable:
WPRO
ABSTRACT
Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.
Palabras clave
Texto completo:
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Base de datos:
WPRIM
Asunto principal:
Semen
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Cilios
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Trastornos de la Motilidad Ciliar
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Dineínas
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Mutación
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Frontiers of Medicine
Año:
2023
Tipo del documento:
Article