ABCMdb

ABCB11 p.Val284Asp

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Publications

PMID: 23022423 [PubMed] Anzivino C et al: "ABCB4 and ABCB11 mutations in intrahepatic cholestasis of pregnancy in an Italian population."

No. Sentence Comment

4 Results: Genotyping revealed 11 mutations, 5 of whom were novel variants: 2 localized on ABCB4 (p.I587DfsX603, p.I738LfsX744) and 3 on ABCB11 (p.V284D, p.Q558H, p.P731S). Login to comment
5 The most severe phenotypes were associated with the variants p.I587DfsX603, p.I738LfsX744 and p.V284D. Login to comment
91 ABCB11 mutation analysis Among the six variants identified in the coding sequence of the ABCB11 gene, three (p.V284D, p.Q558H, p.P731S) were new mutations. Login to comment
92 Variants p.E135K, p.D482G and p.R698H were reported in previous studies [12,25-28]. Login to comment
94 The first novel variant (c.851 T > A), localized in exon 6 at position 284 of BSEP protein (p.V284D), was identified in a 30 years old patient (n.7). Login to comment
101 Nucleotide change and effect on protein Location PSIC scores by PolyPhen-2 analysis Reference 1 c.217 C > G (p. L73V) Exon 4 0.489 [12] 2 c.523 A > G (p.T175A) Exon 6 0.774 [12] 3 c.1529 A > G (p.N510S) Exon 13 2.075 [24] 4 c.1758 1759 ins G (p.I587DfsX603) Exon 15 X This study 5 c.2211(+1) G > T (p.I738LfsX744) 5 Intron 17 X This study ABCB11 mutations 6 c.403 G > A (p.E135K) Exon 6 0.502 [26] 7 c.852 T > A (p.V284D) Exon 9 2.175 This study 8 c.1445 A > G (p.D482G) Exon 14 1.364 [26-28] 9 c.1674 G > C (p.Q558H) Exon 15 1.383 This study 10 c.2093 G > A (p.R698H) Exon 18 0.821 [12,25] 11 c.2191 C > T (p. P731S) Exon 19 0.851 This study New mutations are shown in bold. Login to comment
129 Table 4 Clinical details of patients with ABCB11 mutations. Parameters Patient 6 E135K Patient7 V284D Patient 8 D482G Patient 9 Q558H Patient 10 R698H Patient 11 P731S Onset of pruritus 3rd trimester 2nd trimester 3rd trimester 2nd trimester 2nd trimester 3rd trimester Parity 2 1 2 2 2 2 Previous ICP Yes Yes Yes No Yes Yes Peak of AST (U/L) 24 92 29 125 244 105 Peak of ALT (U/L) 26 215 37 315 514 198 Peak of Bilirubin (mg/dL) 0.53 0.49 Nd 0.36 0.3 0.46 Peak of GGT (U/L) 7 25 Nd 23 14 16 Total bile acids (òe;mol/L) 93.6 112.4 28 Nd 20.4 23.4 Delivery Induction of labour (36w+4 )a Caesarean section (38w)a Induction of labour (38w+4 )a Caesarean section (36w)a Caesarean section (38w)a Induction of labour (38w) Cholelithiasis No No No No No No UDCA therapy Yes Yes No Yes Yes Yes AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: ॹ-glutamyl transpeptidase; Nd: not determined. a Caesarean section or induction of labour due to pregnancy complications related to ICP (foetal distress and/or intolerable pruritus and/or persistent elevation of AST and ALT). Login to comment
145 The p.V284D mutation determines a substitution of a valine with an aspartic acid; the different nature of the aminoacids and its localization in the intracellular loop between transmembrane domain 4 and 5 might lead to an alteration in protein conformation and/or function. Login to comment
146 A further demonstration of the importance of the conservation of this valine in the evolution comes from previous evidence which identified other substitutions in the same position (p.V284L and p.V284A) [12,25,29] and analysed them by the mean of an in vitro minigene system reporting no protein formation for the variant p.V284L and an increased amount of protein for the SNP p.V284A [26]. Login to comment
95 The first novel variant (c.851 T > A), localized in exon 6 at position 284 of BSEP protein (p.V284D), was identified in a 30 years old patient (n.7). Login to comment
102 Nucleotide change and effect on protein Location PSIC scores by PolyPhen-2 analysis Reference 1 c.217 C > G (p. L73V) Exon 4 0.489 [12] 2 c.523 A > G (p.T175A) Exon 6 0.774 [12] 3 c.1529 A > G (p.N510S) Exon 13 2.075 [24] 4 c.1758 1759 ins G (p.I587DfsX603) Exon 15 X This study 5 c.2211(+1) G > T (p.I738LfsX744) 5 Intron 17 X This study ABCB11 mutations 6 c.403 G > A (p.E135K) Exon 6 0.502 [26] 7 c.852 T > A (p.V284D) Exon 9 2.175 This study 8 c.1445 A > G (p.D482G) Exon 14 1.364 [26-28] 9 c.1674 G > C (p.Q558H) Exon 15 1.383 This study 10 c.2093 G > A (p.R698H) Exon 18 0.821 [12,25] 11 c.2191 C > T (p. P731S) Exon 19 0.851 This study New mutations are shown in bold. Login to comment
130 Table 4 Clinical details of patients with ABCB11 mutations. Parameters Patient 6 E135K Patient7 V284D Patient 8 D482G Patient 9 Q558H Patient 10 R698H Patient 11 P731S Onset of pruritus 3rd trimester 2nd trimester 3rd trimester 2nd trimester 2nd trimester 3rd trimester Parity 2 1 2 2 2 2 Previous ICP Yes Yes Yes No Yes Yes Peak of AST (U/L) 24 92 29 125 244 105 Peak of ALT (U/L) 26 215 37 315 514 198 Peak of Bilirubin (mg/dL) 0.53 0.49 Nd 0.36 0.3 0.46 Peak of GGT (U/L) 7 25 Nd 23 14 16 Total bile acids (òe;mol/L) 93.6 112.4 28 Nd 20.4 23.4 Delivery Induction of labour (36w+4 )a Caesarean section (38w)a Induction of labour (38w+4 )a Caesarean section (36w)a Caesarean section (38w)a Induction of labour (38w) Cholelithiasis No No No No No No UDCA therapy Yes Yes No Yes Yes Yes AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: ॹ-glutamyl transpeptidase; Nd: not determined. a Caesarean section or induction of labour due to pregnancy complications related to ICP (foetal distress and/or intolerable pruritus and/or persistent elevation of AST and ALT). Login to comment