19 December 2018

Miriam Schmidts, theme Renal disorders, and colleagues, discovered that recessive DNAH9 loss-of-function mutations cause laterality defects and subtle respiratory ciliary-beating defects. Their exciting findings are published in the American Journal of Human Genetics.

Publication: Link.

Dysfunction of motile monocilia, altering the leftward flow at the embryonic node essential for determination of left-right body asymmetry, is a major cause of laterality defects. Laterality defects are also often associated with reduced mucociliary clearance caused by defective multiple motile cilia of the airway and are responsible for destructive airway disease. Outer dynein arms (ODAs) are essential for ciliary beat generation, and human respiratory cilia contain different ODA heavy chains (HCs): the panaxonemally distributed γ-HC DNAH5, proximally located β-HC DNAH11 (defining ODA type 1), and the distally localized β-HC DNAH9 (defining ODA type 2). Here they report loss-of-function mutations in DNAH9 in five independent families causing situs abnormalities associated with subtle respiratory ciliary dysfunction. Consistent with the observed subtle respiratory phenotype, high-speed video microscopy demonstrates distally impaired ciliary bending in DNAH9 mutant respiratory cilia. DNAH9-deficient cilia also lack other ODA components such as DNAH5, DNAI1, and DNAI2 from the distal axonemal compartment, demonstrating an essential role of DNAH9 for distal axonemal assembly of ODAs type 2. Yeast two-hybrid and co-immunoprecipitation analyses indicate interaction of DNAH9 with the ODA components DNAH5 and DNAI2 as well as the ODA-docking complex component CCDC114. They further showed that during ciliogenesis of respiratory cilia, first proximally located DNAH11 and then distally located DNAH9 is assembled in the axoneme.They proposed that the β-HC paralogs DNAH9 and DNAH11 achieved specific functional roles for the distinct axonemal compartments during evolution with human DNAH9 function matching that of ancient β-HCs such as that of the unicellular Chlamydomonas reinhardtii.

Related news items


Research Integrity Round 16 September 2020 Sex and gender and research integrity: a tale of how and who

9 July 2020

Topic of this webinar is sex and gender in (bio)medical research. Speakers are dean Prof. Jan Smit, Prof. Sabine Oertelt–Prigione and Prof. Hanneke Takkenberg (ErasmusMC). All junior and senior researchers are invited to join the discussion. Please register via the website.

read more

Finally, an explanation for hearing loss in twelve Dutch families

9 July 2020

The culprit is a genetic abnormality, a discovery that immediately makes it one of the most common causes of hereditary hearing loss in the Netherlands.

read more

Symposium ENABLE 2020 postponed to spring 2021

9 July 2020

Considering the COVID-19 pandemic, the ENABLE team decided to postpone the symposium to spring 2021!

read more

Rebecca Halbach receives idea generator grant to fight mosquito transmitted viruses

8 July 2020

Rebecca Halbach and Pascal Miesen have investigated in a collaborative project whether the treatment of mosquitoes with antiviral drugs can prevent the transmission of mosquito-transmitted viral diseases.

read more

Invasive fungal infections in influenza and COVID-19

8 July 2020

The Aspergillus fungus is found in the lungs of many COVID patients. A parallel occurs with influenza patients, who often develop a serious fungal infection. Although such a serious fungal infection seems to occur less frequently in COVID-patients, alertness remains necessary,

read more

Werner Koopman 25 years at Radboudumc celebrating online

8 July 2020

Werner Koopman completed his 25 years at Radboudumc. Biochemistry sent him a cake at home and celebrated this special moment during COVID-19 in a unique way.

read more