title: ZMYND10--Mutation Analysis in Slavic Patients with Primary Ciliary Dyskinesia.
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.
authors.affiliation: Department of Molecular and Clinical Genetics, Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland.|International Institute of Molecular and Cell Biology, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Kurkowiak
authors.affiliation: Department of Molecular and Clinical Genetics, Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Ziętkiewicz
authors.affiliation: Department of Molecular and Clinical Genetics, Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Greber
authors.affiliation: Department of Molecular and Clinical Genetics, Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Voelkel
authors.affiliation: Department of Molecular and Clinical Genetics, Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland.
authors.forename: Alina
authors.initials: A
authors.lastname: Wojda
authors.affiliation: Department of Pneumology and Cystic Fibrosis, Institute of Tuberculosis and Lung Diseases, Rabka Zdrój, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pogorzelski
authors.affiliation: Department of Molecular and Clinical Genetics, Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland.|International Institute of Molecular and Cell Biology, Warsaw, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Witt
mesh_terms: D001483:Base Sequence; D002923:Cilia / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins; D004398:Dyneins / Q000235:genetics / Q000378:metabolism; D005260:Female; D016368:Frameshift Mutation; D015870:Gene Expression; D005808:Genes, Recessive; D018740:Genetic Heterogeneity; D006720:Homozygote; D006801:Humans; D007619:Kartagener Syndrome / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D011044:Poland; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D044465:White People
chemical_list: D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C472720:ZMYND10 protein, human; D004398:Dyneins
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