ABCMdb

PMID: 12717091

Goto K, Sugiyama K, Sugiura T, Ando T, Mizutani F, Terabe K, Ban K, Togari H
Bile salt export pump gene mutations in two Japanese patients with progressive familial intrahepatic cholestasis.
J Pediatr Gastroenterol Nutr. 2003 May;36(5):647-50., [PubMed]

Sentences

No. Mutations Sentence Comment

72 ABCB11 p.Arg575* ABCB11 p.Glu636Gly ABCB11 p.Glu636Gly Of the remaining three substitutions, two were also seen in some control subjects, whereas E636G was not seen in any of the control subjects. Results of genetic analyses performed on family members revealed that R575X was paternal in origin, whereas E636G was maternal in origin. None of these mutations were observed in the asymptomatic brother. Login to comment 73 ABCB11 p.Val444Ala Table 3 summarizes the findings for patient 2. Comparison of cDNA sequences between the patient and the reference revealed five base sequence differences, resulting in four amino acid substitutions. Of the four substitutions, one was a nonsense mutation, and three were missense substitutions. Of the missense substitutions, V339L was found in all control subjects, and V444A was identified in some control subjects. Login to comment 74 ABCB11 p.Arg487His ABCB11 p.Arg487His However, R487H was not observed in any control subjects. Results of genetic analyses performed on family members revealed that V330X was paternal in origin, whereas R487H was maternal in origin. Login to comment 82 ABCB11 p.Val444Ala ABCB11 p.Arg575* ABCB11 p.Glu636Gly ABCB11 p.Ala865Val Differences between BSEP mRNA sequence of Case 1 and registered sequence, and results of genetic analyses performed on family members Nucleotide number of reference sequence Nucleotide substitutions from reference sequence Type of nucleotide Amino acid substitutions from reference sequence Familial investigation of nucleotide substitutions Frequency of alleles of non-PFIC cases 1015 G → C G Val → Leu 0/10 homo C (V339L) 10/10 1331 T → C T Val → Ala 2/10 hetero C (V444A) 8/10 1723 C → T C Arg → Stop Patient: CT Father: CT 10/10 hetero T (R575X) Mother: CC Brother: CC 0/10 1907 A → G A Glu → Gly Patient: AG Father: AA 110/110 hetero G (E636G) Mother: AG Brother: AA 0/100 2594 C → T C Ala → Val 106/110 hetero T (A865V) 4/110 3084 A → G A (-) 5/10 homo G 5/10 A, adenine; T, thymine; G, guanine; C, cytosine; Val, V, valine; Leu, L, Leucine; Ala, A, alanine; Arg, R, arginine; Glu, E, glutamate; Gly, G, glycine; homo, homozygote; hetero, heterozygote. Login to comment 86 ABCB11 p.Arg575* ABCB11 p.Glu636Gly The R575X mutation seen in patient 1 of the present study is a nonsense mutation in the first nucleotide binding fold of the BSEP protein, whereas the E636G mutation is a missense mutation located between the first nucleotide binding fold and the seventh transmembrane domain. Login to comment 87 ABCB11 p.Arg487His ABCB11 p.Trp330* Conversely, the W330X mutation in patient 2 is a nonsense mutation believed to be located in the fifth transmembrane domain of the BSEP protein, whereas R487H is a missense mutation located in the first nucleotide binding fold. Login to comment