ABCMdb

PMID: 21119540

Colombo C, Vajro P, Degiorgio D, Coviello DA, Costantino L, Tornillo L, Motta V, Consonni D, Maggiore G
Clinical features and genotype-phenotype correlations in children with progressive familial intrahepatic cholestasis type 3 related to ABCB4 mutations.
J Pediatr Gastroenterol Nutr. 2011 Jan;52(1):73-83., [PubMed]

Sentences

No. Mutations Sentence Comment

56 ABCB4 p.Gly70Arg Of the 2 missense mutations reported here for the first time, one is novel (c.208G>C, p.G70R) and the other has already been described (c.217C>G, p.L73 V) (22). Login to comment 58 ABCB4 p.Pro726Thr ABCB4 p.Leu701Pro The functional effect of the other 25 missense mutations was evaluated by PolyPhen algorithm (21): 9 mutations (7 inducing amino acid changes in fully conserved nucleotide binding domains and 2 involving the proline residues in the linker region [p.L701P] or transmembrane 7 segment [p.P726T]) gave a PSIC score >2.0 and were defined as probably damaging; 5 mutations with PSIC scores between 1.5 and 2.0 were defined as possibly damaging. Login to comment 107 ABCB4 p.Arg590Gln ABCB4 p.Arg590Gln ABCB4 p.Arg590Gln ABCB4 p.Arg590Gln ABCB4 p.Thr175Ala ABCB4 p.Thr175Ala ABCB4 p.Thr175Ala ABCB4 p.Thr775Met ABCB4 p.Ser320Phe ABCB4 p.Ser320Phe ABCB4 p.Ser320Phe ABCB4 p.Ser320Phe ABCB4 p.Ser320Phe ABCB4 p.Ser320Phe ABCB4 p.Ser320Phe ABCB4 p.Gly70Arg ABCB4 p.Gly70Arg ABCB4 p.Gly70Arg ABCB4 p.Pro726Thr ABCB4 p.Leu701Pro ABCB4 p.Ala511Thr ABCB4 p.Ala511Thr ABCB4 p.Ala364Val ABCB4 p.Ala250Pro ABCB4 p.Glu558Lys ABCB4 p.Glu558Lys ABCB4 p.Ala737Val ABCB4 p.Ala286Val ABCB4 p.Ala1193Thr ABCB4 p.Ala1193Thr ABCB4 p.Glu888* ABCB4 p.Tyr403His ABCB4 p.Tyr403His ABCB4 p.Tyr403His ABCB4 p.Phe357Leu ABCB4 p.Gly954Ser ABCB4 p.Gly954Ser ABCB4 p.Leu73Val ABCB4 p.Gly723Glu ABCB4 p.Gly723Glu ABCB4 p.Tyr279* ABCB4 p.Thr715Ile ABCB4 p.Val475Ala ABCB4 p.Gly762* ABCB4 p.Met630Val ABCB4 p.Ala840Asp ABCB4 p.Arg159* ABCB4 p.Arg159* ABCB4 p.Gly126Glu ABCB4 p.Gly126Glu ABCB4 p.Thr593Ala Nucleotidechange (effectonprotein) Predictionscoresby PolyPhenanalysis Nucleotidechange (effectonprotein) Predictionscoresby PolyPhenanalysis Referencefor eachgenotype 1[1-I]c.475C>T(p.R159X)XUnknownUnknown20 1[1-II]c.475C>T(p.R159X)XUnknownUnknownThisstudy 2[2-I]c.523A>G(p.T175A)0.774c.1069T>C(p.F357L)þc.2324C>T(p.T775M)1.079þ0.59720 3[3-I]c.1135_1136insAA(p.S379KfsX413)Xc.2102T>C(p.L701P)2.22620 4[4-I]c.2662G>T(p.E888X)Xc.748G>C(p.A250P)Rc.1888A>G(p.M630V)1.871R1.67720 5[5-I]c.959C>T(p.S320F)1.287c.857C>T(p.A286V)1.40820 6[6-I]c.377G>A(p.G126E)1.998c.1531G>A(p.A511T)2.1720 6[6-II]c.377G>A(p.G126E)1.998c.1531G>A(p.A511T)2.1720 7[7-I]c.2176C>A(p.P726T)2.086c.1769G>A(p.R590Q)þc.2284G>T(p.G762X)2.623RX20 8[8-1]c.1091C>T(p.A364V)1.343c.2210C>T(p.A737V)0.21720 9[9-I]c.1777A>G(p.T593A)2.044UnknownUnknown20 10[10-I]c.2144C>T(p.T715I)0.383UnknownUnknown20 11[11-I]c.2519C>A(p.A840D)1.803c.1424T>C(p.V475A)2.60320 12[12-I]c.1672G>A(p.E558K)2.486c.2168G>A(p.G723E)Rc.3577G>A(p.A1193T)1.548þ2.34120 12[12-II]c.1672G>A(p.E558K)2.486c.2168G>A(p.G723E)Rc.3577G>A(p.A1193T)1.548þ2.34120 13[13-I]c.2860G>A(p.G954S)0.245c.2860G>A(p.G954S)0.24520 14[14-I]c.523A>G(p.T175A)0.774UnknownUnknown20 15[15-I]c.959C>T(p.S320F)1.287c.837T>A(p.Y279X)X20 16[16-I]c.523A>G(p.T175A)0.774UnknownUnknown20 17[17-I]c.2169_2170insG(p.L724AfsX744)Xc.2169_2170insG(p.L724AfsX744)X20 17[17-II]c.2169_2170insG(p.L724AfsX744)Xc.2169_2170insG(p.L724AfsX744)X20 18[18-I]c.1207T>C(p.Y403H)2.798c.1207T>C(p.Y403H)2.79820 19[19-I]c.208G>C(p.G70R)þc.1769G>A(p.R590Q)1.497þ2.623c.959C>T(p.S320F)1.287Thisstudy 19[19-II]c.208G>C(p.G70R)þc.1769G>A(p.R590Q)1.497þ2.623c.959C>T(p.S320F)1.287Thisstudy 19[19-III]c.208G>C(p.G70R)þc.1769G>A(p.R590Q)1.497þ2.623c.959C>T(p.S320F)1.287Thisstudy 20[20-I]c.217C>G(p.L73V)0.489UnknownUnknown22,thisstudy 21[21-I]c.959C>T(p.S320F)1.287c.959C>T(p.S320F)1.28716,thisstudy 22[22-I]c.1207T>C(p.Y403H)2.798UnknownUnknownThisstudy Xidentifiesmutationsthatpredictprematureterminationoftranslation.PolyPhenpredictionwithPSICscoredifferencesbelow1.5definebenignsubstitutions;PSICscoredifferencesencompassing between1.5and2.0(bold)definesubstitutionspossiblydamaging,whereasabove2.0(underlined)definesubstitutionsprobablydamaging. Login to comment 108 ABCB4 p.Ser320Phe substitution p.S320F in 3 cases. Login to comment 128 ABCB4 p.Tyr403His This may be the case for patient 18-I, who had moderate ABCB4 immunostaining (60% of the cells, Fig. 2) and was homozygous for the missense mutation p.Y403H. Login to comment 131 ABCB4 p.Arg652Gly Distribution of ABCB4 SNPs in 68 patients with chronic intrahepatic cholestasis without ABCB4 mutations and 112 healthy subjects ABCB4 genotypes ABCB4 alleles SNPsÃ NCBI annotation Location Patients Controls Fisher P Patients Controls Fisher Pwt het homo wt het homo Allele 1 Allele 2 Allele 1 Allele 2 c.175 C>T (p.L59L) rs2302387 Exon 4 48 19 1 57 26 3 0.72 115 21 140 32 0.54 c.287-61 C>T rs45626341 Intron 4 64 4 0 97 5 0 1.00 132 4 199 5 1.00 c.504 T>C (p.N168N) rs1202283 Exon 6 13 36 19 28 56 20 0.29 62 74 112 96 0.15 c.711 A>T (p.I237I) rs2109505 Exon 8 48 17 3 66 37 3 0.34 113 23 169 43 0.48 c.834-66 G>T rs1014283 Intron 8 46 19 3 63 37 3 0.50 111 25 163 43 0.68 c.1231-81 delT rs3834727 Intron 11 58 8 1 94 6 0 0.15 124 10 194 6 0.07 c.1357-40 G>A Not annotated Intron 12 54 13 1 92 18 0 0.45 121 15 202 18 0.45 c.1954 A>G (p.R652G) rs2230028 Exon 16 59 8 1 94 15 0 0.47 126 10 203 15 1.00 c.2064þ55 A>G rs1017054 Intron 16 59 8 1 94 15 0 0.47 126 10 203 15 1.00 c.2211þ16 T>C rs31668 Intron 17 54 13 1 86 17 0 0.45 121 15 189 17 0.45 c.2478þ40 A>G rs788404 Intron 20 59 7 2 87 11 0 0.30 125 11 185 11 0.38 c.2479-66 delG rs5885584 Intron 20 59 7 2 91 17 0 0.11 125 11 199 17 1.00 c.2683-197 T>C rs17149547 Intron 21 59 7 2 85 11 0 0.34 125 11 181 11 0.50 c.3508-16 C>T rs31653 Intron 26 54 13 1 88 18 1 0.85 121 15 194 20 0.71 c.3655-72 T>C rs45549641 Intron 27 60 6 2 81 11 0 0.24 126 10 173 11 0.65 Ã Positions are based on translation start site of ATG (NM_018849). Login to comment