ABCMdb

PMID: 12891548

Rosmorduc O, Hermelin B, Boelle PY, Parc R, Taboury J, Poupon R
ABCB4 gene mutation-associated cholelithiasis in adults.
Gastroenterology. 2003 Aug;125(2):452-9., [PubMed]

Sentences

No. Mutations Sentence Comment

63 ABCB4 p.Arg590Gln ABCB4 p.Gly742Ser However, because these mutations affected nonconserved amino acids between the human ABCB4 gene and its rodent homologs, they were not considered as DCMs.13, 14 They were localized in the third intracellular loop and in the fourth extracellular loop of the protein (e.g., Arg590Gln and Gly742Ser). Login to comment 67 ABCB4 p.Arg652Gly A previously described Arg652Gly SNP was detected at a similar frequency (approximately 5%) in patients with and Table 3. Login to comment 68 ABCB4 p.Thr175Ala ABCB4 p.Glu528Asp ABCB4 p.Ser320Phe ABCB4 p.Ala934Thr ABCB4 p.Phe165Ile ABCB4 p.Met301Thr ABCB4 p.Arg788Glu ABCB4 p.Leu591Gln ABCB4 Gene Mutations in Patients With LPAC Syndrome Gene position Location and nucleotide change Peptide change Protein domain Status 6 495T3A Phe165Ile First intracellular loop Heterozygous 523T3C Thr175Ala between TM2 and TM3 Heterozygous 9 902T3C Met301Thr TM5 Heterozygous 959C3T Ser320Phe TM5 Homozygous 10 1007-1015insT 355Stop TM6 Heterozygous 1007-1015delT 341Stop TM6 Heterozygous 12 1327insA 447Stop Close to NBD11 Heterozygous 14 1584G3C Glu528Asp Close to NBD11 Heterozygous 15 1772T3A Leu591Gln Third intracellular loop Homozygous 17 1973G3A Try658Stop Third intracellular loop linker domain Heterozygous 18 2270-2273insT 793Stop Fourth intracellular loop between TM8 and TM9 Heterozygous 19 2363G3T Arg788Glu Fourth intracellular loop between TM8 and TM9 Heterozygous 23 2800G3T Ala934Thr Fifth intracellular loop between TM10 and TM11 Homozygous 26 3481C3T Pro1161Ser Close to NBD2 Heterozygous NOTE. The A of ATG of the initiator Met codon was denoted as "nucleotide ϩ 1." Login to comment 90 ABCB4 p.Arg652Gly Characterization of ABCB4 Gene SNPs and Determination of the Main Allele Frequency in Patients With and Without LPAC Syndrome and in Control Subjects SNP1 SNP2 SNP3 SNP4 SNP5 SNP characteristics SNP localization Exon 4 Exon 5 Exon 6 Exon 8 Exon 16 Nucleotide change 175C3T 342T3C 504C3T 711A3T 1954A3G Amino acid Leu59 Thr114 Asn168 Ile237 Arg652Gly Most frequent allele CTG ACT AAC ATA AGG Group of patients and controls Mutation, LPAC phenotype (score Ն2) 21/24 (87.5%) 24/24 (100%) 16/30 (53.3%) 21/24 (87.5%) 23/24 (95.8%) No mutation, LPAC phenotype (score Ն2) 27/28 (96.4%) 27/28 (96.4%) 3/28 (10.7%) 27/28 (96.4%) 27/28 (96.4%) No mutation, no LPAC phenotype (score Ͻ2) 52/56 (92.8%) 56/56 (100%) 29/56 (51.8%) 51/56 (91.1%) 51/56 (91.1%) Control subjects 54/66 (81.8%) 65/66 (98.5%) 36/66 (54.5%) 50/66 (89.3%) 61/66 (92.4%) Bonferroni-adjusted P value (5 comparisons) 0.05 0.99 0.001 0.14 0.99 NOTE. The table indicates the most frequent allele to total number of alleles ratio for each tested SNP in the different groups of patients. Login to comment 96 ABCB4 p.Thr175Ala ABCB4 p.Thr175Ala ABCB4 p.Glu528Asp Two of the missense mutations (Thr175Ala and Glu528Asp) detected in the patients with the LPAC syndrome were analyzed previously in yeast.23,24 The Thr175Ala mutation was localized in the first intracellular loop and resulted in a substitution in a conserved cluster of 4 amino acids at position 169-172, which is required for the adenosine triphosphatase activity of the molecule. Login to comment 98 ABCB4 p.Phe165Ile The Phe165Ile mutation was localized in the same part of this intracellular loop and might thereby give rise to a similar defect. Login to comment 99 ABCB4 p.Glu528Asp The Glu528Asp mutation was localized close to the NBD1. Login to comment 102 ABCB4 p.Thr175Ala The 2 unrelated patients in whom the Thr175Ala mutation was identified originated from Northern Europe, so they may have inherited a founder mutation from a shared ancestor. Login to comment 105 ABCB4 p.Ser320Phe ABCB4 p.Ala934Thr In addition, the LPAC syndrome was observed in patients with similar nonsense or missense mutations: in a mother and her elder son with an identical heterozygous nonsense mutation (1327insA); in patients from nonconsanguineous families with the same homozygous missense mutation (Ser320Phe or Ala934Thr) with asymptomatic heterozygous parents; in patients with a similar nonsense mutation (1006-1016insT and 1006-1016delT); and in unrelated patients with the same missense mutations (Pro1161Ser). Login to comment 106 ABCB4 p.Ser320Phe In addition, the S320F mutation was recently identified in a patient who presented with ICP and cholelithiasis.5 For these reasons, all these mutations could be considered as causing the LPAC syndrome. Login to comment