PMID- 10577904
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20181113
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 6
DP  - 1999 Dec
TI  - Loss-of-function mutations in a human gene related to Chlamydomonas reinhardtii
      dynein IC78 result in primary ciliary dyskinesia.
PG  - 1508-19
AB  - Primary ciliary dyskinesia (PCD) is a group of heterogeneous disorders of unknown
      origin, usually inherited as an autosomal recessive trait. Its phenotype is
      characterized by axonemal abnormalities of respiratory cilia and sperm tails
      leading to bronchiectasis and sinusitis, which are sometimes associated with
      situs inversus (Kartagener syndrome) and male sterility. The main ciliary defect 
      in PCD is an absence of dynein arms. We have isolated the first gene involved in 
      PCD, using a candidate-gene approach developed on the basis of documented
      abnormalities of immotile strains of Chlamydomonas reinhardtii, which carry
      axonemal ultrastructural defects reminiscent of PCD. Taking advantage of the
      evolutionary conservation of genes encoding axonemal proteins, we have isolated a
      human sequence (DNAI1) related to IC78, a C. reinhardtii gene encoding a dynein
      intermediate chain in which mutations are associated with the absence of outer
      dynein arms. DNAI1 is highly expressed in trachea and testis and is composed of
      20 exons located at 9p13-p21. Two loss-of-function mutations of DNAI1 have been
      identified in a patient with PCD characterized by immotile respiratory cilia
      lacking outer dynein arms. In addition, we excluded linkage between this gene and
      similar PCD phenotypes in five other affected families, providing a clear
      demonstration of locus heterogeneity. These data reveal the critical role of
      DNAI1 in the development of human axonemal structures and open up new means for
      identification of additional genes involved in related developmental defects.
FAU - Pennarun, G
AU  - Pennarun G
AD  - Institut National de la Sante et de la Recherche Medicale U468, Hopital
      Henri-Mondor, 94010 Creteil, France.
FAU - Escudier, E
AU  - Escudier E
FAU - Chapelin, C
AU  - Chapelin C
FAU - Bridoux, A M
AU  - Bridoux AM
FAU - Cacheux, V
AU  - Cacheux V
FAU - Roger, G
AU  - Roger G
FAU - Clement, A
AU  - Clement A
FAU - Goossens, M
AU  - Goossens M
FAU - Amselem, S
AU  - Amselem S
FAU - Duriez, B
AU  - Duriez B
LA  - eng
SI  - GENBANK/AF063228
SI  - GENBANK/AF063229
SI  - GENBANK/AF063231
SI  - GENBANK/AF070687
SI  - GENBANK/AF190477
SI  - GENBANK/AF190478
SI  - GENBANK/AF190479
SI  - GENBANK/AF190480
SI  - GENBANK/AF190481
SI  - GENBANK/AF190482
SI  - GENBANK/AF190483
SI  - GENBANK/AF190484
SI  - GENBANK/AF190485
SI  - GENBANK/AF190486
SI  - GENBANK/AF190487
SI  - GENBANK/AF190488
SI  - GENBANK/AF190489
SI  - GENBANK/AF190490
SI  - GENBANK/AF190491
SI  - GENBANK/AF190492
SI  - GENBANK/AF190493
SI  - GENBANK/AF190494
SI  - GENBANK/AF190495
SI  - GENBANK/AF190496
SI  - GENBANK/D38538
SI  - GENBANK/U19120
SI  - GENBANK/U25116
SI  - GENBANK/U39044
SI  - GENBANK/X55382
SI  - GENBANK/X66845
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - EC 3.6.4.2 (Dyneins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Child
MH  - Chlamydomonas reinhardtii/chemistry/*genetics
MH  - Chromosomes, Human, Pair 9/genetics
MH  - Cilia/pathology/ultrastructure
MH  - Ciliary Motility Disorders/*genetics/pathology
MH  - Cloning, Molecular
MH  - Consanguinity
MH  - Dyneins/chemistry/*genetics/ultrastructure
MH  - Female
MH  - Gene Expression Profiling
MH  - Genetic Heterogeneity
MH  - Genetic Linkage/genetics
MH  - Humans
MH  - Male
MH  - Molecular Sequence Data
MH  - Mutation/*genetics
MH  - Phylogeny
MH  - Physical Chromosome Mapping
MH  - Polymorphism, Single-Stranded Conformational
MH  - Sequence Homology, Amino Acid
PMC - PMC1288361
EDAT- 1999/12/01 09:00
MHDA- 2000/03/21 09:00
CRDT- 1999/12/01 09:00
PHST- 1999/12/01 09:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/12/01 09:00 [entrez]
AID - S0002-9297(07)63570-8 [pii]
AID - 10.1086/302683 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Dec;65(6):1508-19. doi: 10.1086/302683.