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ZMYND10--Mutation Analysis in Slavic Patients with Primary Ciliary Dyskinesia
Małgorzata Kurkowiak1,2, Ewa Ziętkiewicz1, Agnieszka Greber1
1Department of Molecular and Clinical Genetics, Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland.
Insights
Researchers identified a novel ZMYND10 gene mutation in Polish primary ciliary dyskinesia (PCD) patients. This frameshift mutation, unique to the Slavic population, offers new diagnostic insights for this rare genetic disorder.
Area of Science:
- Genetics
- Rare Diseases
- Cell Biology
Background:
- Primary ciliary dyskinesia (PCD) is a rare genetic disorder affecting cilia function, impacting respiratory, reproductive, and embryonic development.
- Genetic heterogeneity exists in PCD, with known genes explaining only 60-65% of cases, necessitating further research into population-specific mutations.
- Slavic populations are underrepresented in PCD genetic studies, limiting diagnostic capabilities.
Purpose of the Study:
- To investigate causative genetic defects in the ZMYND10 gene within a cohort of Slavic (Polish) primary ciliary dyskinesia patients.
- To identify novel mutations in ZMYND10 specific to the Slavic PCD population.
Main Methods:
- Screening of 172 unrelated Polish PCD patients negative for mutations in nine major PCD genes.
- High-resolution melting (HRM) analysis for mutation screening.
- Immunofluorescence and cDNA analysis to confirm mutation effects on ciliary structure and gene expression.
Main Results:
- A novel homozygous frameshift mutation (c.367delC) in the ZMYND10 gene was identified in two unrelated Polish PCD patients.
- This mutation was not previously described and appears unique to the Slavic PCD population.
- Immunofluorescence confirmed the absence of dynein arms, and cDNA analysis indicated nonsense-mediated decay of ZMYND10 mRNA.
Conclusions:
- The identified c.367delC mutation in ZMYND10 is a novel cause of primary ciliary dyskinesia in the Slavic population.
- This finding expands the spectrum of genetic defects underlying PCD and improves diagnostic potential for Slavic patients.
- The study highlights the importance of investigating population-specific genetic variations in rare diseases.
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.
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