PMID- 10053008
OWN - NLM
STAT- MEDLINE
DCOM- 19990420
LR  - 20211203
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 64
IP  - 3
DP  - 1999 Mar
TI  - Genomic structure of the canalicular multispecific organic anion-transporter gene
      (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson
      syndrome.
PG  - 739-46
AB  - Dubin-Johnson syndrome (DJS) is an autosomal recessive disease characterized by
      conjugated hyperbilirubinemia. Previous studies of the defects in the human
      canalicular multispecific organic anion transporter gene (MRP2/cMOAT) in patients
      with DJS have suggested that the gene defects are responsible for DJS. In this
      study, we determined the exon/intron structure of the human MRP2/cMOAT gene and
      further characterized mutations in patients with DJS. The human MRP2/cMOAT gene
      contains 32 exons, and it has a structure that is highly conserved with that of
      another ATP-binding-cassette gene, that for a multidrug resistance-associated
      protein. We then identified three mutations, including two novel ones. All
      mutations identified to date are in the cytoplasmic domain, which includes the
      two ATP-binding cassettes and the linker region, or adjacent putative
      transmembrane domain. Our results confirm that MRP2/cMOAT is the gene responsible
      for DJS. The finding that mutations are concentrated in the first
      ATP-binding-cassette domain strongly suggests that a disruption of this region is
      a critical route to loss of function.
FAU - Toh, S
AU  - Toh S
AD  - Department of Biochemistry, Kyushu University School of Medicine, Maidashi 3-1-1,
      Fukuoka 812-8582, Japan.
FAU - Wada, M
AU  - Wada M
FAU - Uchiumi, T
AU  - Uchiumi T
FAU - Inokuchi, A
AU  - Inokuchi A
FAU - Makino, Y
AU  - Makino Y
FAU - Horie, Y
AU  - Horie Y
FAU - Adachi, Y
AU  - Adachi Y
FAU - Sakisaka, S
AU  - Sakisaka S
FAU - Kuwano, M
AU  - Kuwano M
LA  - eng
SI  - GENBANK/U63970
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  - 0 (ABCC2 protein, human)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Anion Transport Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Coproporphyrins)
RN  - 0 (DNA Primers)
RN  - 0 (Multidrug Resistance-Associated Protein 2)
RN  - 531-14-6 (coproporphyrin I)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - ATP-Binding Cassette Transporters/*genetics
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Amino Acid Sequence
MH  - Anion Transport Proteins
MH  - Base Sequence
MH  - Bilirubin/blood
MH  - Carrier Proteins/*genetics
MH  - Coproporphyrins/urine
MH  - DNA Mutational Analysis
MH  - DNA Primers
MH  - Exons
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Introns
MH  - Jaundice, Chronic Idiopathic/*genetics
MH  - Male
MH  - Middle Aged
MH  - Models, Genetic
MH  - Molecular Sequence Data
MH  - Multidrug Resistance-Associated Protein 2
MH  - Phenotype
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC1377791
EDAT- 1999/03/03 03:04
MHDA- 2000/03/21 09:00
CRDT- 1999/03/03 03:04
PHST- 1999/03/03 03:04 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/03/03 03:04 [entrez]
AID - S0002-9297(07)61711-X [pii]
AID - 10.1086/302292 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Mar;64(3):739-46. doi: 10.1086/302292.