ABCB4 p.Arg150Lys
| Predicted by SNAP2: | A: D (85%), C: D (85%), D: D (95%), E: D (91%), F: D (91%), G: D (91%), H: D (85%), I: D (91%), K: D (80%), L: D (91%), M: D (80%), N: D (91%), P: D (91%), Q: D (80%), S: D (85%), T: D (85%), V: D (91%), W: D (95%), Y: D (91%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: N, L: D, M: D, N: D, P: D, Q: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Intrahepatic cholestasis of pregnancy: three novel... Aliment Pharmacol Ther. 2006 Jun 1;23(11):1649-53. Floreani A, Carderi I, Paternoster D, Soardo G, Azzaroli F, Esposito W, Variola A, Tommasi AM, Marchesoni D, Braghin C, Mazzella G
Intrahepatic cholestasis of pregnancy: three novel MDR3 gene mutations.
Aliment Pharmacol Ther. 2006 Jun 1;23(11):1649-53., [PMID:16696816]
Abstract [show]
BACKGROUND: The aetiology of intrahepatic cholestasis of pregnancy is unknown, but more than 10 different MDR3 gene mutations have recently been identified. AIM: To evaluate the genetic contribution of the MDR3 gene in the pathogenesis of intrahepatic cholestasis of pregnancy in Italian subjects. METHODS: We performed a multicentre prospective case-control study, enrolling 80 women with intrahepatic cholestasis of pregnancy at the third trimester of pregnancy and 80 pregnant women without intrahepatic cholestasis of pregnancy. Genomic DNA was extracted from peripheral venous blood leucocytes using standard procedures. The polymerase chain reaction was used to amplify exon 14 of the MDR3 gene and the polymerase chain reaction products were sequenced using a Big Dye Terminator Cycle Sequencing kit. RESULTS: Three novel non-synonymous heterozygous mutations in exon 14 were found (4%; E528D, R549H, G536R) among the 80 intrahepatic cholestasis of pregnancy patients, whereas the pregnant controls were all negative for exon 14 polymorphisms. The three patients involved had normal GGT and bilirubin, but high levels of both ALT and serum bile acids. One had cholesterol bile stones. The outcome of pregnancy was normal for two (with vaginal delivery), while foetal distress was recorded in the third. CONCLUSIONS: These three novel mutations add further information on the involvement of the MDR3 gene in intrahepatic cholestasis of pregnancy. As in other studies, we found only heterozygous mutations that could cause an impaired transport protein function, not its absence (which is responsible for more severe liver disease). Different genetic backgrounds might justify the presence of novel MDR3 gene mutations.
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No. Sentence Comment
35 MDR3 mutations reported in the literature Mutation (codon) Exon Reference (R144X) 6 Gendrot et al.5 481G>A (R150K) 6 Mu¨llenbach et al.6 426-432del (132) 6 DeVree et al.13 959C>T (S320F) 9 Rosmordurc et al.,14 Pauli-Magnus et al.9 (G535D) 14 Lucena et al.7 1669 C>A (A546D) 14 Dixon et al.4 1712 del T (571) 14 Jacquemin et al.8, 15 2285 G>A (G762E) 18 Pauli-Magnus et al.9 2901 C>T (R957X) 23 DeVree et al.13 conditions included an initial denaturation step at 94 °C for 5 min, followed by 40 cycles of denaturation at 94 °C for 30 s, annealing at 55 °C for 30 s and extension at 72 °C for 30 s.
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ABCB4 p.Arg150Lys 16696816:35:108
status: NEW[hide] ABCB4 gene sequence variation in women with intrah... J Med Genet. 2003 May;40(5):e70. Mullenbach R, Linton KJ, Wiltshire S, Weerasekera N, Chambers J, Elias E, Higgins CF, Johnston DG, McCarthy MI, Williamson C
ABCB4 gene sequence variation in women with intrahepatic cholestasis of pregnancy.
J Med Genet. 2003 May;40(5):e70., [PMID:12746424]
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148 • We have identified a new variant R150K that segregates with ICP in a UK pedigree and that is present in one additional case.
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ABCB4 p.Arg150Lys 12746424:148:42
status: NEW195 The only exceptions are 959C>T, which has been described in two patients with gallstones and ICP from two independent, non-consanguineous families,19 and the 481G>A (R150K) mutation reported in this study.
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ABCB4 p.Arg150Lys 12746424:195:166
status: NEW218 ABCB4 R150K may have a direct effect specific to the binding of phosphatidylcholine.
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ABCB4 p.Arg150Lys 12746424:218:6
status: NEW226 In summary, the current study has identified a new mutation (R150K) that cosegregates with ICP in a UK pedigree and an unrelated case.
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ABCB4 p.Arg150Lys 12746424:226:61
status: NEW227 However, no functional effect was shown when R150K was expressed in P-gp1.
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ABCB4 p.Arg150Lys 12746424:227:45
status: NEW