title: MDR3 mutations associated with intrahepatic and gallbladder cholesterol cholelithiasis: an update.
abstract: BACKGROUND
  The recurrent microlithiasis represents one of the most frequent clinical forms of lithiasis of the bile ducts. This affection is characterized by the presence of cholesterolic microgallstones on hepatic canaliculars, and belongs to a heterogeneous group of autosomal recessive liver disorders. Radiological diagnosis can be confirmed by analysis of MDR3 gene, coding a protein involved in physiologic translocation of phospholipids in bile. Discovery of MDR3 mutations is of particular interest, since normally associated with good effectiveness of medication by ursodesoxycholic acid.
  
  
  OBJECTIVE
  To review MDR3 mutations in humans associated with recurrent cholesterol microlithiasis and to suggest a practical approach for MDR3 gene analysis.
  
  
  RESULTS
  48 mutations of MDR3 gene have been reported in humans to date, from which 43 (89.5%) in the coding region, and 5 splice site mutations have been associated to cholesterol cholelithiasis. 21 (43.8%) of the 43 precited mutations are located in only 8 exons on 28, near transmembrane or nucleotide binding domains of the protein. From the 22 remaining described mutations, 9 (18.8%) are restricted to exon 14. We suggest therefore to start analysis of MDR3 gene by screening exons 6, 7, 9, 10, 12, 14, 17, 23 and 24 with an appropriate protocol in this diagnosis associated with effective treatment. In conclusion such therapeutic orientation is valuable, since recurrent cholesterolic microlithiasis occurs relatively early in life, and by the fact that recurrence of symptoms may occur despite cholecystectomy, or shock-wave therapy.
authors.affiliation: BEGIN Military Hospital, Department of Biochemistry, Saint-Mandé, France.
authors.forename: Elvire
authors.initials: E
authors.lastname: Mbongo-Kama
authors.forename: Florence
authors.initials: F
authors.lastname: Harnois
authors.forename: Didier
authors.initials: D
authors.lastname: Mennecier
authors.forename: Eleonore
authors.initials: E
authors.lastname: Leclercq
authors.forename: Pascal
authors.initials: P
authors.lastname: Burnat
authors.forename: Franck
authors.initials: F
authors.lastname: Ceppa
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D041761:Cholecystolithiasis / Q000235:genetics* / Q000378:metabolism; D042883:Choledocholithiasis / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D005704:Gallbladder / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D009154:Mutation / Q000235:genetics