ABCB4 p.Arg582Gln
| Predicted by SNAP2: | A: D (80%), C: D (63%), D: D (95%), E: D (91%), F: D (91%), G: D (91%), H: D (75%), I: D (85%), K: D (80%), L: D (91%), M: D (75%), N: D (91%), P: D (91%), Q: D (85%), S: D (85%), T: D (85%), V: D (85%), W: D (91%), Y: D (91%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, S: D, T: D, V: D, W: D, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[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.
Comments [show]
None has been submitted yet.
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.Arg582Gln 22343912:6:116
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.Arg582Gln 22343912:76:126
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.Arg582Gln 22343912:83:156
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.Arg582Gln 22343912:87:188
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.Arg582Gln 22343912:88:243
status: NEW92 MDR3 staining was completely absent with compound heterozygous mutations c.139C>T (p.R47X) and c.1745G>A (p.R582Q) (case 13, Fig. 1E).
X
ABCB4 p.Arg582Gln 22343912:92:108
status: NEW144 Normal MDR3 staining (A) and normal BSEP staining (B) in control liver specimen; normal MDR3 staining (C) and normal BSEP staining (D) in case 6 without ABCB4 mutation; absence of MDR3 staining (E) and normal BSEP staining (F) in case 13 with compound heterozygous ABCB4 mutations c.139C>T (p.R47X) and c.1745G>A (p.R582Q); faint MDR3 staining (G) and normal BSEP staining (H) in case 11 with compound heterozygous ABCB4 mutations c.
X
ABCB4 p.Arg582Gln 22343912:144:316
status: NEW