ABCMdb

PMID: 23142591

Davit-Spraul A, Gonzales E, Jacquemin E
NR1H4 analysis in patients with progressive familial intrahepatic cholestasis, drug-induced cholestasis or intrahepatic cholestasis of pregnancy unrelated to ATP8B1, ABCB11 and ABCB4 mutations.
Clin Res Hepatol Gastroenterol. 2012 Dec;36(6):569-73. doi: 10.1016/j.clinre.2012.08.008. Epub 2012 Nov 9., [PubMed]

Sentences

No. Mutations Sentence Comment

55 ABCB11 p.Val444Ala ABCB11 p.Val444Ala ABCB11 p.Val444Ala ABCB11 p.Val444Ala ABCB11 p.Val444Ala ABCB11 p.Val444Ala ABCB11 p.Met677Val ABCB11 p.Met677Val Table 1 Main clinical characteristics and ATP8B1, ABCB11 and NR1H4 genotypes in eight normal GGT PFIC patients of unknown cause. Patient Phenotype ATP8B1 genotype ABCB11 genotype NR1H4 genotype Liver histology and canalicular immunostaining Patient 1 Severe permanent cholestasis since age 5 mo, Serum BS = 208 òe;mol/L, deafness, UDCA and BD not tested, LT at 4.5 yr, alive at 25 yr No mutation p.V444A Heterozygous No mutation Hepatocellular cholestasis, septal fibrosis BSEP+ MDR3+ Patient 2 Severe permanent cholestasis since age 1 mo, Serum BS = 161 òe;mol/L, Biliary BS = 5.7 mmol/L, Success of UDCA but persistent pruritus Alive at 5 yr p.R952Q Heterozygous p.V444A, p.M677V Heterozygous No mutation Hepatocellular cholestasis, septal fibrosis BSEP+ MDR3+ Patient 3 Severe recurrent cholestasis since age 7 mo, Serum BS = 375 òe;mol/L, Biliary BS = 0.39 mmol/L, Success of UDCA, then of BD at 7.5 yr, Chronic diarrhea, and liver steatosis post BD, Alive at 19 yr p.R952Q Heterozygous No mutation No mutation Hepatocellular cholestasis, septal fibrosis BSEP+ MDR3+ Patient 4 Severe permanent cholestasis since age 1 mo, Serum BS = 291 òe;mol/L, UDCA failure, BD not tested, LT at 3.2 yr, died post-LT p.R952Q Heterozygous p.V444A Heterozygous No mutation Hepatocellular cholestasis, septal fibrosis BSEP+ MDR3+ Patient 5 Severe cholestasis since age 3 mo, Serum BS = 262 òe;mol/L, UDCA failure, BD success at 4.7 yr, Alive at 14 yr p.R952Q Heterozygous p.V444A Heterozygous No mutation Hepatocellular cholestasis, septal fibrosis BSEP+ MDR3+ Patient 6 Severe permanent cholestasis since age 1 mo, Serum BS = 191 òe;mol/L, biliary BS = 0.09 mmol/L, TC = 7 mmol/L, TG = 4.5 mmol/L, UDCA and BD failure, LT at 6 yr, died post-LT No mutation No mutation No mutation Hepatocellular cholestasis, septal fibrosis BSEP+ MDR3+ Patient 7 Cholestasis since age 2.5 yr, Serum BS = 42 òe;mol/L, Success of UDCA, Alive at 20 yr No mutation p.M677V, p.G319G Homozygous p.V444A Heterozygous No mutation Hepatocellular cholestasis, septal fibrosis BSEP+ MDR3+ Patient 8 Severe cholestasis since age 1 week, Serum BS = 240 òe;mol/L, UDCA and BD not tested, Liver failure and LT at age 5 mo, Alive at 21 yr No mutation p.V444A Heterozygous No mutation Hepatocellular cholestasis, septal fibrosis Giant cells BSEP-, MDR3+ GGT: gammaglutamyl transferase; PFIC: progressive familial intrahepatic cholestasis; BS: bile salt concentration; UDCA: ursodeoxycholic acid; BD: biliary diversion; LT: liver transplantation; mo: month; yr: year; BSEP+: normal immunostaining; BSEP-: negative immunostaining; MDR3+: normal immunostaining; TC: serum fasting total cholesterol; TG: serum fasting triglycerides. Login to comment 59 ABCB11 p.Val444Ala ABCB11 p.Val444Ala ABCB11 p.Val444Ala ABCB11 p.Val444Ala Table 2 Main clinical characteristics and ATP8B1, ABCB11, ABCB4 and NR1H4 genotypes in eight patients with normal or elevated GGT ICP or DIC of unknown cause. Patient Phenotype ATP8B1 genotype ABCB11 genotype ABCB4 genotype NR1H4 genotype Patient 9 DIC (OP): P, I, ALT = 3ULN, GGT = N. Normalisation after OP withdrawal Sister: cytolysis and P under OP, ICP Grand mother: cholecystitis No mutation No mutation No mutation No mutation Patient 10 ICP: P, I, discoloured stools, GGT = N, ALT = 18ULN, Ultrasonography: biliary sludge No mutation p.V444A Homozygous No mutation No mutation Patient 11 ICP: P, GGT = N, serum BS 270 òe;M, in utero fetal death No mutation p.V444A Homozygous No mutation No mutation Patient 12 ICP: P, GGT = N, ALT = N Mother: ICP No mutation p.V444A Homozygous No mutation No mutation Patient 13 DIC (OP): I, P, biliary lithiasis with recurrence after cholecystectomy GGT = 14ULN, ALT = 20ULN Not done p.V444A Heterozygous No mutation No mutation Patient 14 ICP: P, GGT = N Daughter: NC (ductular paucity) elevated GGT Mother: chronic cholestasis, P, elevated GGT No mutation No mutation No mutation No mutation Patient 15 ICP: P, elevated GGT Not done Not done No mutation No mutation Patient 16 ICP: P, GGT = 4ULN, DIC (PTU): P, GGT = 8ULN, ALT = 33ULN, GL = 7.8 mmol/L, CT = 7.3 mmol/L, TG = 1.64 mmol/L Not done Not done No mutation c-1G > T Heterozygous ICP: intrahepatic cholestasis of pregnancy; DIC: drug-induced cholestasis; OP: oestroprogestatif; PTU: propylthiouracil; NC: neonatal cholestasis; GGT: serum gammaglutamyl transferase; N: normal; ULN: fold the upper limit of normal; BS: bile salt concentration; ALT: serum alanine aminotransferase; TC: serum fasting total cholesterol; TG: serum fasting triglycerides; Glc: fasting glycemia; P: pruritus; I: icterus. Login to comment 60 ABCB11 p.Val444Ala ABCB11 p.Val444Ala ABCB11 p.Val444Ala ABCB11 p.Val444Ala Normalisation after OP withdrawal Sister: cytolysis and P under OP, ICP Grand mother: cholecystitis No mutation No mutation No mutation No mutation Patient 10 ICP: P, I, discoloured stools, GGT = N, ALT = 18ULN, Ultrasonography: biliary sludge No mutation p.V444A Homozygous No mutation No mutation Patient 11 ICP: P, GGT = N, serum BS 270 òe;M, in utero fetal death No mutation p.V444A Homozygous No mutation No mutation Patient 12 ICP: P, GGT = N, ALT = N Mother: ICP No mutation p.V444A Homozygous No mutation No mutation Patient 13 DIC (OP): I, P, biliary lithiasis with recurrence after cholecystectomy GGT = 14ULN, ALT = 20ULN Not done p.V444A Heterozygous No mutation No mutation Patient 14 ICP: P, GGT = N Daughter: NC (ductular paucity) elevated GGT Mother: chronic cholestasis, P, elevated GGT No mutation No mutation No mutation No mutation Patient 15 ICP: P, elevated GGT Not done Not done No mutation No mutation Patient 16 ICP: P, GGT = 4ULN, DIC (PTU): P, GGT = 8ULN, ALT = 33ULN, GL = 7.8 mmol/L, CT = 7.3 mmol/L, TG = 1.64 mmol/L Not done Not done No mutation c-1G > T Heterozygous ICP: intrahepatic cholestasis of pregnancy; DIC: drug-induced cholestasis; OP: oestroprogestatif; PTU: propylthiouracil; NC: neonatal cholestasis; GGT: serum gammaglutamyl transferase; N: normal; ULN: fold the upper limit of normal; BS: bile salt concentration; ALT: serum alanine aminotransferase; TC: serum fasting total cholesterol; TG: serum fasting triglycerides; Glc: fasting glycemia; P: pruritus; I: icterus. 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