ABCMdb

ABCB11 p.Ala257Gly

Reviews:	p.Ala257Gly D
Predicted by SNAP2:	C: D (59%), D: D (75%), E: D (71%), F: D (59%), G: N (87%), H: D (66%), I: D (59%), K: D (71%), L: D (66%), M: D (53%), N: D (63%), P: D (80%), Q: D (66%), R: D (71%), S: N (57%), T: N (78%), V: D (59%), W: D (80%), Y: D (66%),
Predicted by PROVEAN:	C: D, D: D, E: D, F: D, G: N, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: N, T: D, V: D, W: D, Y: D,

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Publications
[hide] ATP8B1 and ABCB11 analysis in 62 children with nor... Hepatology. 2010 May;51(5):1645-55. Davit-Spraul A, Fabre M, Branchereau S, Baussan C, Gonzales E, Stieger B, Bernard O, Jacquemin E
ATP8B1 and ABCB11 analysis in 62 children with normal gamma-glutamyl transferase progressive familial intrahepatic cholestasis (PFIC): phenotypic differences between PFIC1 and PFIC2 and natural history.
Hepatology. 2010 May;51(5):1645-55., [PMID:20232290]

Abstract [show]
Progressive familial intrahepatic cholestasis (PFIC) types 1 and 2 are characterized by normal serum gamma-glutamyl transferase (GGT) activity and are due to mutations in ATP8B1 (encoding FIC1) and ABCB11 (encoding bile salt export pump [BSEP]), respectively. Our goal was to evaluate the features that may distinguish PFIC1 from PFIC2 and ease their diagnosis. We retrospectively reviewed charts of 62 children with normal-GGT PFIC in whom a search for ATP8B1 and/or ABCB11 mutation, liver BSEP immunostaining, and/or bile analysis were performed. Based on genetic testing, 13 patients were PFIC1 and 39 PFIC2. The PFIC origin remained unknown in 10 cases. PFIC2 patients had a higher tendency to develop neonatal cholestasis. High serum alanine aminotransferase and alphafetoprotein levels, severe lobular lesions with giant hepatocytes, early liver failure, cholelithiasis, hepatocellular carcinoma, very low biliary bile acid concentration, and negative BSEP canalicular staining suggest PFIC2, whereas an absence of these signs and/or presence of extrahepatic manifestations suggest PFIC1. The PFIC1 and PFIC2 phenotypes were not clearly correlated with mutation types, but we found tendencies for a better prognosis and response to ursodeoxycholic acid (UDCA) or biliary diversion (BD) in a few children with missense mutations. Combination of UDCA, BD, and liver transplantation allowed 87% of normal-GGT PFIC patients to be alive at a median age of 10.5 years (1-36), half of them without liver transplantation. CONCLUSION: PFIC1 and PFIC2 differ clinically, biochemically, and histologically at presentation and/or during the disease course. A small proportion of normal-GGT PFIC is likely not due to ATP8B1 or ABCB11 mutations.

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Sentences [show]
No. Sentence Comment
102 12† p.T1210P p.T1210P 0.11 BSEP À PFIC2 no. 13 c.3213 15 G>A p.A1192EfsX50 na BSEP À PFIC2 no. Login to comment
105 20† p.A257G p.G982R na na PFIC2 no. 21* p.I182K c.3213 15 G>A na BSEP À PFIC2 no. 22 p.D549V c.76 13 G>T na na PFIC2 no. Login to comment