ZMYND10--Mutation Analysis in Slavic Patients with Primary Ciliary Dyskinesia

Autor: Agnieszka Greber, Małgorzata Kurkowiak, Michał Witt, Andrzej Pogorzelski, Alina Wojda, Katarzyna Voelkel, Ewa Ziętkiewicz
Rok vydání: 2015
Předmět:
0301 basic medicine
Male
RNA Stability
lcsh:Medicine
Gene Expression
Artificial Gene Amplification and Extension
medicine.disease_cause
Biochemistry
Polymerase Chain Reaction
Database and Informatics Methods
0302 clinical medicine
lcsh:Science
Frameshift Mutation
Primary ciliary dyskinesia
Genetics
Mutation
education.field_of_study
Multidisciplinary
Cilium
Homozygote
Complementary DNA
Phenotype
3. Good health
Pedigree
Nucleic acids
Motile cilium
Female
Cellular Structures and Organelles
Sequence Analysis
Research Article
Forms of DNA
Population
Molecular Sequence Data
Sequence Databases
Genes
Recessive
Biology
Research and Analysis Methods
White People
Frameshift mutation
03 medical and health sciences
Genetic Heterogeneity
Extraction techniques
medicine
otorhinolaryngologic diseases
Humans
Cilia
RNA
Messenger
education
Molecular Biology Techniques
Sequencing Techniques
Molecular Biology
Base Sequence
Genetic heterogeneity
Kartagener Syndrome
Tumor Suppressor Proteins
lcsh:R
Dyneins
Biology and Life Sciences
DNA
Cell Biology
medicine.disease
RNA extraction
Cytoskeletal Proteins
030104 developmental biology
Biological Databases
030228 respiratory system
Mutation Databases
lcsh:Q
Poland
Zdroj: PLoS ONE
PLoS ONE, Vol 11, Iss 1, p e0148067 (2016)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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