ABCB4 p.Val526Phe
| Predicted by SNAP2: | A: D (66%), C: D (59%), D: D (85%), E: D (85%), F: D (75%), G: D (85%), H: D (85%), I: N (61%), K: D (85%), L: D (59%), M: D (66%), N: D (85%), P: D (85%), Q: D (80%), R: D (85%), S: D (80%), T: D (75%), W: D (85%), Y: D (80%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, W: D, Y: D, |
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[hide] ABCB4 heterozygous gene mutations associated with ... Gastroenterology. 2008 Jul;135(1):131-41. Epub 2008 Mar 26. Ziol M, Barbu V, Rosmorduc O, Frassati-Biaggi A, Barget N, Hermelin B, Scheffer GL, Bennouna S, Trinchet JC, Beaugrand M, Ganne-Carrie N
ABCB4 heterozygous gene mutations associated with fibrosing cholestatic liver disease in adults.
Gastroenterology. 2008 Jul;135(1):131-41. Epub 2008 Mar 26., [PMID:18482588]
Abstract [show]
BACKGROUND & AIMS: Adenosine triphosphate-binding cassette subfamily B, member 4 (ABCB4) mutations have not been investigated in patients with unexplained cholestasis. We aimed to investigate ABCB4 mutations in adult patients with unexplained anicteric cholestasis and to describe liver injury associated with ABCB4 mutations. METHODS: Between February 2004 and March 2007, all adults with unexplained cholestasis despite multiple investigations including liver biopsy and 124 healthy volunteers had ABCB4 sequencing. Fibrosis, bile duct lesions, inflammatory infiltrate, activation of myofibroblasts and multidrug-resistant P-glycoprotein 3 (MDR3) immunostaining were assessed on patients' liver biopsy specimens. RESULTS: Thirty-two patients were included (23 females, 16-69 years of age). Eight different ABCB4 heterozygous mutations were found in 11 patients (34%). Seven of these mutations (exons 4, 6, 14, 18, 23) were never detected in the control group. One mutation (exon 15) was detected in 4 patients (12.5%) and 4 controls (3%). At the time of liver biopsy, the main clinical and biologic characteristics were similar in the 32 patients regardless of ABCB4 mutation. The histologic pattern in patients with a mutation consisted of portal fibrosis with ductular reaction and strong macrophagic infiltrate of portal tracts without significant periportal and lobular necroinflammatory lesions or cholangitis. Fibrosis score and macrophagic infiltration of portal tracts were significantly increased in patients with ABCB4 mutation (P = .01). Absence or reduced MDR3 canalicular immunostaining was demonstrated in all patients with ABCB4 mutations tested. CONCLUSIONS: Heterozygous ABCB4 mutations were detected in 34% of adults with unexplained cholestasis, for the most part without biliary symptoms, and could result in significant liver fibrosis.
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56 As described in Figure 1, 3 (T175A, R590Q, A934T) have been previously described in patients with LPAC or ICP.8,13 Conversely, 5 (R47X, V526F, A539T, R545G, I738L) have not been previously described.20 The frequency of each mutation is indicated in Figure 1.
X
ABCB4 p.Val526Phe 18482588:56:136
status: NEW95 1576GϾT V526F aICP (intrahepatic cholestasis of pregnancy).
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ABCB4 p.Val526Phe 18482588:95:14
status: NEW57 As described in Figure 1, 3 (T175A, R590Q, A934T) have been previously described in patients with LPAC or ICP.8,13 Conversely, 5 (R47X, V526F, A539T, R545G, I738L) have not been previously described.20 The frequency of each mutation is indicated in Figure 1.
X
ABCB4 p.Val526Phe 18482588:57:136
status: NEW96 1576Gb0e;T V526F aICP (intrahepatic cholestasis of pregnancy).
X
ABCB4 p.Val526Phe 18482588:96:14
status: NEW