ABCB4 p.Asp459Gly
| Predicted by SNAP2: | A: D (71%), C: D (75%), E: D (71%), F: D (85%), G: D (80%), H: D (80%), I: D (85%), K: D (85%), L: D (85%), M: D (80%), N: N (72%), P: D (80%), Q: D (75%), R: D (85%), S: D (71%), T: D (80%), V: D (80%), W: D (85%), Y: D (85%), |
| Predicted by PROVEAN: | A: D, C: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Chinese children with chronic intrahepatic cholest... J Pediatr Gastroenterol Nutr. 2012 Aug;55(2):150-6. Fang LJ, Wang XH, Knisely AS, Yu H, Lu Y, Liu LY, Wang JS
Chinese children with chronic intrahepatic cholestasis and high gamma-glutamyl transpeptidase: clinical features and association with ABCB4 mutations.
J Pediatr Gastroenterol Nutr. 2012 Aug;55(2):150-6., [PMID:22343912]
Abstract [show]
OBJECTIVE: The aims of the present study was to study the significance of ABCB4 mutations in mainland Chinese children with chronic intrahepatic cholestasis and to correlate genetic findings with clinical features and response to ursodeoxycholic acid (UDCA) therapy. METHODS: Thirteen patients with chronic intrahepatic cholestasis and elevated serum gamma-glutamyl transpeptidase activity of unknown cause were enrolled in a single pediatric center. All of the encoding exons and flanking areas of ABCB4 were sequenced. Available liver biopsy specimens were immunostained for multidrug resistance protein 3. The clinical features, biochemical parameters, and responses to therapy were compared with patients with or without ABCB4 mutation(s). RESULTS: Six different ABCB4 mutations were identified in 3 patients; each patient was a compound heterozygote. Apart from c.139C>T (p.R47X), all were novel, including c.344+2_+3insT, c.1376A>G (p.D459G), c.1745G>A (p.R582Q), c.2077_2078delC (p.P693HfsX698), and c.3825_3826delA (p.M1276WfsX1308). Absent or reduced multidrug resistance protein 3 canalicular immunostaining was demonstrated in patients with ABCB4 mutations. Serum total bile acid levels were higher in patients with ABCB4 mutations than in patients without ABCB4 mutations (352.5 +/- 97.0 vs 55.9 +/- 50.4 mumol/L, P = 7.32E-05). There was no difference in other biochemical parameters between patients with and without ABCB4 mutations. After oral UDCA administration in 3 patients with ABCB4 mutations, pruritus disappeared, growth improved, spleen size decreased, and platelet counts increased. In the 10 patients without ABCB4 mutations, an inconsistent response to UDCA therapy was observed. CONCLUSIONS: In mainland Chinese children, some cases of chronic intrahepatic cholestasis with high gamma-glutamyl transpeptidase could be attributed to ABCB4 mutations. UDCA administration partially improved clinical symptoms and liver function.
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No. Sentence Comment
6 Apart from c.139C>T (p.R47X), all were novel, including c.344þ2_þ3insT, c.1376A>G (p.D459G), c.1745G>A (p.R582Q), c.2077_2078delC (p.P693HfsX698), and c.3825_3826delA (p.M1276WfsX1308).
X
ABCB4 p.Asp459Gly 22343912:6:95
status: NEW76 Apart from c.139C>T (p.R47X) (19), they were novel; they included c.344þ2_þ3insT, c.1376A>G (p.D459G), c.1745G>A (p.R582Q), c.2077_2078delC (p.P693HfsX698), and c.3825_3826delA (p.M1276WfsX1308).
X
ABCB4 p.Asp459Gly 22343912:76:105
status: NEW83 Amino acid residues in the first highly conserved nucleotide-binding domains (NBDs) (residues 404-630) are affected by c.1376A>G (p.D459G) and c.1745G>A (p.R582Q).
X
ABCB4 p.Asp459Gly 22343912:83:132
status: NEW87 The absolute differences between the 2 profile score sets are 1.988 and 2.468, respectively, indicating that c.1376A>G (p.D459G) is likely to affect protein function and that c.1745G>A (p.R582Q) is able to affect protein function.
X
ABCB4 p.Asp459Gly 22343912:87:122
status: NEW88 ESE Finder predicted c.1376A>G (p.D459G) to decrease the splicing-factor score at a SF (splicing factor)2/alternative splicing factor (ASF)-binding site (from 3.960444 to 3.233662) and to abolish a SC35-binding site; it predicted c.1745G>A (p.R582Q) to enhance the splicing-factor score at a SF2/ASF-binding site (from 3.317899 to 3.765121), to abolish a SF2/ASF-binding site, and to generate a new SRp40-binding site.
X
ABCB4 p.Asp459Gly 22343912:88:34
status: NEW93 Faint MDR3 staining was found with compound heterozygous mutations c.1376A>G (p.D459G) and M1276WfsX1308 (case 11, Fig. 1G).
X
ABCB4 p.Asp459Gly 22343912:93:80
status: NEW145 3825_3826delA (p.M1276WfsX1308) and c.1376A>G (p.D459G).
X
ABCB4 p.Asp459Gly 22343912:145:49
status: NEW