ABCB4 p.Pro741Leu
| Predicted by SNAP2: | A: N (87%), C: N (82%), D: N (78%), E: N (87%), F: N (66%), G: N (78%), H: N (78%), I: N (82%), K: N (93%), L: N (82%), M: N (82%), N: N (93%), Q: N (93%), R: N (82%), S: N (93%), T: N (93%), V: N (82%), W: D (59%), Y: N (78%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, Q: N, R: N, S: N, T: N, V: N, W: D, Y: N, |
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[hide] ABCB4 mutations underlie hormonal cholestasis but ... World J Gastroenterol. 2014 May 21;20(19):5867-74. doi: 10.3748/wjg.v20.i19.5867. Jirsa M, Bronsky J, Dvorakova L, Sperl J, Smajstrla V, Horak J, Nevoral J, Hrebicek M
ABCB4 mutations underlie hormonal cholestasis but not pediatric idiopathic gallstones.
World J Gastroenterol. 2014 May 21;20(19):5867-74. doi: 10.3748/wjg.v20.i19.5867., [PMID:24914347]
Abstract [show]
AIM: To investigate the contribution of ABCB4 mutations to pediatric idiopathic gallstone disease and the potential of hormonal contraceptives to prompt clinical manifestations of multidrug resistance protein 3 deficiency. METHODS: Mutational analysis of ABCB4, screening for copy number variations by multiplex ligation-dependent probe amplification, genotyping for low expression allele c.1331T>C of ABCB11 and genotyping for variation c.55G>C in ABCG8 previously associated with cholesterol gallstones in adults was performed in 35 pediatric subjects with idiopathic gallstones who fulfilled the clinical criteria for low phospholipid-associated cholelithiasis syndrome (LPAC, OMIM #600803) and in 5 young females with suspected LPAC and their families (5 probands, 15 additional family members). The probands came to medical attention for contraceptive-associated intrahepatic cholestasis. RESULTS: A possibly pathogenic variant of ABCB4 was found only in one of the 35 pediatric subjects with idiopathic cholesterol gallstones whereas 15 members of the studied 5 LPAC kindreds were confirmed and another one was highly suspected to carry predictably pathogenic mutations in ABCB4. Among these 16, however, none developed gallstones in childhood. In 5 index patients, all young females carrying at least one pathogenic mutation in one allele of ABCB4, manifestation of LPAC as intrahepatic cholestasis with elevated serum activity of gamma-glutamyltransferase was induced by hormonal contraceptives. Variants ABCB11 c.1331T>C and ABCG8 c.55G>C were not significantly overrepresented in the 35 examined patients with suspect LPAC. CONCLUSION: Clinical criteria for LPAC syndrome caused by mutations in ABCB4 cannot be applied to pediatric patients with idiopathic gallstones. Sexual immaturity even prevents manifestation of LPAC.
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No. Sentence Comment
73 In patient 31, a novel heterozygous variation was found (c.2222C>T, leading to predicted conservative amino acid substitution p.Pro741Leu in the extracellular loop between transmembrane domains 7 and 8).
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ABCB4 p.Pro741Leu 24914347:73:128
status: NEW72 In patient 31, a novel heterozygous variation was found (c.2222C>T, leading to predicted conservative amino acid substitution p.Pro741Leu in the extracellular loop between transmembrane domains 7 and 8).
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ABCB4 p.Pro741Leu 24914347:72:128
status: NEW