title: Identification of a novel 2026G-->C mutation of the MRP2 gene in a Japanese patient with Dubin-Johnson syndrome.
abstract: Dubin-Johnson syndrome is a recessive inherited disorder with conjugated hyperbilirubinemia caused by a dysfunction of multidrug resistance protein 2 (MRP2) on the canalicular membrane of hepatocytes. A mutational analysis of the MRP2 gene was carried out in three Japanese patients and their family members. In two patients, the homozygous mutations c.1901del67 and c,2272del168 were found. In the third patient, a -24C-->T polymorphism and the two mutations c.1901del67 and 2026G-->C were detected. The 2026G-->C mutation was a novel mutation in exon 16 affecting the conversion of Gly(676) to Arg(676) (G676R) in the MRP2 protein, and was not detected in fifty healthy volunteers. The G676R mutation was located in the Walker A motif of the first nucleotide binding domain in the MRP2 protein, and it was suggested that the mutation induced the dysfunction of the MRP2 protein. It was concluded that the compound heterozygosity of the two mutations of the MRP2 gene in the third patient contributed to the induction of hyperbilirubinemia in this case.
authors.affiliation: Department of Medicine, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa 920-1181, Japan. s-wakusawa@hokuriku-u.ac.jp.
authors.forename: Shinya
authors.initials: S
authors.lastname: Wakusawa
authors.affiliation: Department of Medicine, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa 920-1181, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Machida
authors.affiliation: Department of Medicine, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa 920-1181, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Medicine, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa 920-1181, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Gastroenterology, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Yano
authors.affiliation: Gastroenterology, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yoshioka
mesh_terms: D000328:Adult; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007564:Japan; D007566:Jaundice, Chronic Idiopathic / Q000235:genetics*; D008297:Male; D024101:Mitochondrial Proteins; D010375:Pedigree; D017354:Point Mutation; D012333:RNA, Messenger; D012269:Ribosomal Proteins / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA
chemical_list: C093947:MRP2 protein, S cerevisiae; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins