skip to main content

New Bestcilia publication: genetic mutations in Slavic patients with PCD

Bestcilia participants associated with the International Institute of Molecular and Cell Biology in Warsaw, Poland (WP7) have recently authored a new and notable publication. The article focuses on the genetic mutations causing PCD in Slavic population. The article is of particular interest as the Slavs have thus far received far less coverage in PCD-related research than Western European populations, which affects the diagnostic capability for this population group.

The research in question follows two publications in the 2013 issue of American Journal of Human Genetics (available in full here and here, hyperlinks here?), which identify mutations of ZMYND10 gene as PCD-causative. The study was carried out on the biological material of as many as 172 unrelated patients of Polish origin.

The researchers used HRM-based screening in search of mutations of any of the 9 most common PCD-related genes. While no such mutations were found, a novel mutation (c.367delC) of the ZMYND10 gene, specific to the Slavic population, was discovered in two individuals. This mutation may possibly be cause of PCD in sufferers of Slavic extraction. It affects the process of protein biosynthesis, generating truncated mRNA and, potentially, truncated and dysfunctional protein. Crucially, further cDNA analysis of ciliated rhinal epithelium revealed the absence of ZYMND10 mRNA, which had probably been degraded in the process of nonsense-mediated decay: an energy-efficient mechanism of the cells, aimed at reducing errors in gene expression by eliminating errant mRNAs. Subsequent immunofluorescence analysis showed lack of expected signal from outer and inner dynein arms of the ciliary axoneme, indicating that the protein was not generated.

The results of the study firmly indicate that the novel mutation may in fact be a cause of PCD in the Polish population, even if it does not belong to the most common ones. They are also consistent with the previous assumptions that PCD-causative gene mutations in the Slavic population differ from those reported for the Western European patients.

Full article is available here.