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

Bart van de Warrenburg appointed visiting professor at the UKM Medical Centre in Kuala Lumpur

11 November 2019

Neurologist and Principal Investigator at the Donders Institute Bart van de Warrenburg has been appointed visiting professor at the UKM Medical Centre in Kuala Lumpur.

read more

KNAW Van Leersum beurs for Mohammad Alsady

7 November 2019

Mohammad Alsady, theme Disorders of movement, received the “KNAW Van Leersum beurs”.

read more

3D breast ultrasound elastography to improve breast cancer detection

5 November 2019

One out of seven women will be diagnosed with breast cancer during their life. Early detection of breast cancer is important to increase the survival rate. Gijs Hendriks graduated recently on a new technique, 3D elastography, to detect breast cancer better.

read more

Self-management rehabilitation program improves participation in patients with neuromuscular disease

4 November 2019

Yvonne Veenhuizen, Alexander Geurts theme Neurorehabilitation, Baziel van Engelen, theme Disorders of movement, and colleagues, showed that Energetic improves participation in patients with neuromuscular disease. They have published their results in Neurology.

read more

New NFU eBROK® course open for registration

1 November 2019

This platform is not only for researchers who want to obtain their BROK® certificate, but also for researchers who already have a BROK® certificate and want to keep their certification (re-certification).

read more

Emily Klooster wins the NVZF incentive prize

31 October 2019

For the second year in a row, a PhD candidate from the Allied Health Sciences group of IQ Healthcare (RIHS), has won the "Dutch Association for Physiotherapists in the Hospital" incentive prize.

read more