Abstract
Primary ciliary dyskinesia (PCD) is a rare recessive disease with a prevalence of 1/10,000; its symptoms are caused by a kinetic dysfunction of motile cilia in the respiratory epithelium, flagella in spermatozoids, and primary cilia in the embryonic node. PCD is genetically heterogeneous: genotyping the already known PCD-related genes explains the genetic basis in 60–65% of the cases, depending on the population. While identification of new genes involved in PCD pathogenesis remains crucial, the search for new, population-specific mutations causative for PCD is equally important. The Slavs remain far less characterized in this respect compared to West European populations, which significantly limits diagnostic capability. The main goal of this study was to characterize the profile of causative genetic defects in one of the PCD-causing genes, ZMYND10, in the cohort of PCD patients of Slavic origin. The study was carried out using biological material from 172 unrelated PCD individuals of Polish origin, with no causative mutation found in nine major PCD genes. While none of the previously described mutations was found using the HRM-based screening, a novel frameshift mutation (c.367delC) in ZMYND10, unique for Slavic PCD population, was found in homozygous state in two unrelated PCD patients. Immunofluorescence analysis confirmed the absence of outer and inner dynein arms from the ciliary axoneme, consistent with the already published ZMYND10-mutated phenotype; cDNA analysis revealed the lack of ZMYND10 mRNA, indicating nonsense-mediated decay of the truncated transcript.
Highlights
Primary ciliary dyskinesia (PCD, OMIM id: 242650), one of the major ciliopathies, is a rare, genetically heterogeneous autosomal recessive disease, caused by the abnormal structure and/or function of motile cilia [1,2]
The high-resolution melt (HRM) technique was used to screen the selected Polish cohort of 172 PCD patients for the presence of seven PCD-causing ZMYND10 mutations previously reported in the Caucasian population
A novel c.367delC frameshift mutation was identified in two homozygous, unrelated PCD patients from different regions of Poland
Summary
Primary ciliary dyskinesia (PCD, OMIM id: 242650), one of the major ciliopathies, is a rare (with a prevalence of 1/10,000), genetically heterogeneous autosomal recessive disease, caused by the abnormal structure and/or function of motile cilia [1,2]. Mutations in 29 genes have been found to underlie PCD pathogenesis in different families (for a recent review see Kurkowiak et al, 2015) [3].
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