Two new genes were discovered recently, that with specific genetic mutations, produce PCD. The two new genes are LRRC56 and DNAH9.

A group of international scientists, Serge Bonnefoy, Christopher Watson, Philippe Bastin, Eamonn Sheridan and colleagues, announced the discovery of a mutation in a new gene, LRRC56, that results in the physical symptoms characteristic of PCD. Patients with the LRRC56 genetic defect displayed neonatal acute respiratory distress following normal term birth, laterality defects, chronic runny nose, chronic cough, and repeated respiratory tract infections leading to development of bronchiectasis at early age. The researchers published a paper describing their discovery of LRRC56 in the November 2018 issue of The American Journal of Human Genetics.

Two independent research groups simultaneously discovered the DNAH9 gene. One group of scientists, Mahmoud Masad, Amelia Shoemark, Hannah Mitchison, and colleagues, discovered the gene using next-generation genetic sequencing in a group of patients from PCD clinics with situs inversus and in one case, male infertility. Electron microscopy revealed defects in the outer dynein arm at the tip of the cilium that resulted in the individuals having reduced airway clearance. The other group of scientists, Niki Loges, Dinu Anthony, Heymut Omran, Miriam Schmidts, and colleagues, discovered loss of function mutations in DNAH5 in five independent families that produced situs abnormalities and impaired ciliary bending in their respiratory cilia. They also saw outer dynein arm abnormalities in this patient group. Both groups of researchers independently published papers describing their discovery of DNAH9 in the December 2018 issue of The American Journal of Human Genetics.

The discovery of LRRC56 and DNAH9 brings the total number of genes with genetic mutations known to cause PCD to 42 and new genetic mutations are being found every year. It is important to note that it will likely be some time before the LRRC56 and DNAH9 mutations are included on any of the commercial PCD genetic panels. On the other hand, both mutations result in defects in the outer dynein arms which increasing defects toward the tip of the cilium. These defects can currently be detected via a good cilia biopsy followed by electron microscopy imaging. Geneticists estimate that the percentage of PCD patients having either mutation will likely be less than 1-2%. Genetic mutations in known genes still account for only about 70% of PCD patients with 30% having genetic mutations yet to be discovered. However, the good news is that these two new discoveries show that we continue to make good progress in our understanding the genetics of PCD.

Richard Vassar
PCD Foundation Board Member