ABCMdb

PMID: 15841457

Keitel V, Burdelski M, Warskulat U, Kuhlkamp T, Keppler D, Haussinger D, Kubitz R
Expression and localization of hepatobiliary transport proteins in progressive familial intrahepatic cholestasis.
Hepatology. 2005 May;41(5):1160-72., [PubMed]

Sentences

No. Mutations Sentence Comment

38 ABCB4 p.Thr175Ala ABCB4 p.Ala953Asp ABCC3 p.Ser346Ile Clinical and Laboratory Parameters of PFIC Patients Patients Clinical Parameters Laboratory Parameters Diagnosis Onset of Symptoms Age at LTx BS (<8 ␮M) ␥GT (<25 U/l) Bilirubin (<1 mg/dL) MDR3-Mutation MDR3- IF BSEP- IF PFIC Type C1 F.A. 4 m 3 y 5 m 47 7 1.3 None detected ϩ - 2 C2 A.A. 3 m 2 y 5 m 144 19 22.6 None detected ϩ - 2 C3 S.H. 3 m 3 y 3 m 616 77 22.7 None detected ϩ - 2 C4 M.D. 6 m 10 y 7 m 160 7 5.4 None detected ϩ - 2 C5 T.A. 6 m 4 y 2 m 414 11 5.4 555 A 3 G/T175A Heterozygous ϩ - 2 C6 M.D. 4 m 7 y 9 m 163 26 11.2 1069 G 3 T/S346I ϩ ϩ 3 C7 S.F. birth 8 y 7 m 299 250 1.9 1069 G 3 T/8346I* ϩ ϩ 3 C8 K.Y. 6 m 3 y 10 m 85 277 0.5 2890 C 3 A/A953D ϩ ϩ 3 C9 K.B. 4 m 3 y 8 m 360 165 1.1 426-432 del† - ϩ 3 C10 B.D. 7 y 11 y 4 m 199 24 20.7 None detected - ϩ 3 NOTE. Login to comment 109 ABCB4 p.Ala953Asp ABCB4 p.Ser346Ile Two different mutations were found in the three patients with detectable canalicular MDR3 immunoreactivity (S346I and A953D). Login to comment 166 ABCB11 p.Asp482Gly Defective BSEP targeting as an important mechanism underlying PFIC-2 was reported recently: 5 of 7 mutations prevented rat Bsep from trafficking to the apical membrane.37 Similarly, increased intracellular degradation and reduced canalicular targeting of mouse Bsep carrying the common D482G mutation was demonstrated recently.38 MDR3 immunofluorescence is of limited value in the diagnosis of PFIC-3, as shown by the association of disease-causing MDR3 mutations and normal canalicular MDR3 localization. Login to comment 167 ABCB4 p.Ser346Ile The mutation S346I was detected in 2 children (C6 and C7). Login to comment 168 ABCB4 p.Ala953Asp Normal canalicular MDR3 localization associated with this mutation was already reported for child C7.39 A second MDR3 mutation (A953D, C8) identified in this study has not been described so far. Login to comment 169 ABCB4 p.Ser346Ile Similar to S346I, a canalicular staining pattern of MDR3 was observed in this patient. Login to comment 170 ABCB4 p.Val425Met ABCB4 p.Thr424Ala Additional PFIC-3 causing MDR3 mutations, which do not prevent MDR3 targeting to the canaliculi, include T424A and V425M.22,39 Preserved expression and targeting suggest that these MDR3 mutations cause decreased transporter activity. Login to comment 185 ABCB4 p.Thr175Ala (PFIC-2 patient C5) results in an amino acid change in codon 175 from threonine to alanine. Login to comment