title: Identification of the human ortholog of the t-complex-encoded protein TCTE3 and evaluation as a candidate gene for primary ciliary dyskinesia.
abstract: Primary ciliary dyskinesia (PCD) is a heterogeneous autosomal recessive disease that is caused by impaired ciliary and flagellar functions. About 50% of PCD patients show situs inversus, denoted as Kartagener syndrome. In most cases, axonemal defects in cilia and sperm tails can be demonstrated by electron microscopy, i.e. PCD patients often lack inner and/or outer dynein arms in their sperm tails and cilia, supporting the hypothesis that mutations in dynein genes may cause PCD. In order to identify novel PCD genes we have isolated the human ortholog of the murine TCTE3 gene. The human TCTE3 gene encodes a dynein light chain and shares high similarity to dynein light chains of other species. The TCTE3 gene is expressed in tissues containing cilia or flagella, it is composed of four exons and located on chromosome 6q25-->q27. To elucidate the role of TCTE3 as a candidate gene for PCD a mutational analysis of thirty-six PCD patients was performed. We detected five polymorphisms in the coding sequence and in the 5' UTR of the TCTE3 gene. In one patient a heterozygous nucleotide exchange was identified resulting in an arginine to isoleucine substitution at the amino acid level. However, this exchange was also detected in one control DNA. Our results indicate that mutations in the TCTE3 gene are not a main cause of primary ciliary dyskinesia.
authors.affiliation: Institute of Human Genetics, University of Göttingen, Germany. jneesen@gwdg.de
authors.forename: J
authors.initials: J
authors.lastname: Neesen
authors.forename: J-D
authors.initials: JD
authors.lastname: Drenckhahn
authors.forename: S
authors.initials: S
authors.lastname: Tiede
authors.forename: P
authors.initials: P
authors.lastname: Burfeind
authors.forename: M
authors.initials: M
authors.lastname: Grzmil
authors.forename: J
authors.initials: J
authors.lastname: Konietzko
authors.forename: C
authors.initials: C
authors.lastname: Dixkens
authors.forename: J
authors.initials: J
authors.lastname: Kreutzberger
authors.forename: F
authors.initials: F
authors.lastname: Laccone
authors.forename: H
authors.initials: H
authors.lastname: Omran
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002925:Ciliary Motility Disorders / Q000235:genetics*; D003001:Cloning, Molecular; D003241:Consanguinity; D056445:Cytoplasmic Dyneins; D017931:DNA Primers; D004398:Dyneins; D005808:Genes, Recessive; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007621:Karyotyping; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D015183:Restriction Mapping; D012617:Sea Urchins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014337:Trout; D044767:Ubiquitin-Protein Ligases; D056427:t-Complex Genome Region
chemical_list: D056445:Cytoplasmic Dyneins; D017931:DNA Primers; D004398:Dyneins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D011506:Proteins; D044767:Ubiquitin-Protein Ligases; C533377:DYNLT2 protein, human; C116196:PPP1R11 protein, human