Identification of the human ortholog of the t-complex-encoded protein TCTE3 and evaluation as a candidate gene for primary ciliary dyskinesia

TY - JOUR

T1 - Identification of the human ortholog of the t-complex-encoded protein TCTE3 and evaluation as a candidate gene for primary ciliary dyskinesia

AU - Neesen, J

AU - Drenckhahn, J-D

AU - Tiede, S

AU - Burfeind, P

AU - Grzmil, M

AU - Konietzko, J

AU - Dixkens, C

AU - Kreutzberger, J

AU - Laccone, F

AU - Omran, H

N1 - Copyright 2002 S. Karger AG, Basel

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Animals

KW - Base Sequence

KW - Chromosome Mapping

KW - Ciliary Motility Disorders

KW - Cloning, Molecular

KW - Consanguinity

KW - Cytoplasmic Dyneins

KW - DNA Primers

KW - Genes, Recessive

KW - Humans

KW - Intracellular Signaling Peptides and Proteins

KW - Karyotyping

KW - Microtubule-Associated Proteins

KW - Molecular Sequence Data

KW - Nuclear Proteins

KW - Polymorphism, Genetic

KW - Proteins

KW - Restriction Mapping

KW - Sea Urchins

KW - Sequence Alignment

KW - Sequence Homology, Amino Acid

KW - Trout

KW - t-Complex Genome Region

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1159/000068545

DO - 10.1159/000068545

M3 - SCORING: Journal article

C2 - 12584439

VL - 98

SP - 38

EP - 44

JO - CYTOGENET GENOME RES

JF - CYTOGENET GENOME RES

SN - 1424-8581

IS - 1

ER -