ABCMdb

PMID: 11313315

Jacquemin E, De Vree JM, Cresteil D, Sokal EM, Sturm E, Dumont M, Scheffer GL, Paul M, Burdelski M, Bosma PJ, Bernard O, Hadchouel M, Elferink RP
The wide spectrum of multidrug resistance 3 deficiency: from neonatal cholestasis to cirrhosis of adulthood.
Gastroenterology. 2001 May;120(6):1448-58., [PubMed]

Sentences

No. Mutations Sentence Comment

57 ABCB4 p.Arg652Gly To detect a polymorphism, a total of 100 control chromosomes were screened by restriction enzyme analysis for the missense mutation R652G, which was found in 5 of the 31 patients. Login to comment 113 ABCB4 p.Arg652Gly ABCB4 p.Arg652Gly R652G Mutation and Polymorphism The nonconservative missense mutation R652G located in the linker region, was identified in 5 affected patients (patients LM, GaM, LH, LF, and VHC), but was found heterozygous with the same frequency in 50 unaffected unrelated healthy individuals (data not shown). Login to comment 121 ABCB4 p.Arg652Gly Among heterozygous parents, 3 mothers had experienced episodes of cholestasis of pregnancy.23,26 These parents were heterozygous for a mutation leading to a premature truncation of the protein in 2 cases and for the R652G missense mutation in 1 case. Login to comment 126 ABCB4 p.Ile541Phe ABCB4 p.Arg652Gly ABCB4 p.Asp564Gly ABCB4 p.Ser346Ile ABCB4 p.Arg957* ABCB4 p.Val425Met ABCB4 p.Trp138Arg ABCB4 p.Phe711Ser ABCB4 p.Glu395Gly ABCB4 p.Leu556Arg ABCB4 p.Gly983Ser ABCB4 p.Gln636* ABCB4 p.Thr424Ala MDR3 Mutations, Immunohistochemistry, and Biliary Phospholipids in Patients With High GGT PFIC (PFIC3) Patients Exon Nucleotide mutation Amino acid change Protein consequence Family MDR3 liver Phospholipids (%) bile Homozygous Deletion/Insertion M Y M I (sister of M Y) 2 111 A Ͼ G, splice donor site, exon/intron boundary 2/3 27 Frame shift in NH2 terminus, then truncation ND Absent ND 1.6 B Ka 6 426-432 del 132 Frame shift in TMD 2, 29 novel amino acids then truncation Mother ϩ/- Father ϩ/- 1 sibling ϩ/ϩ Absent ND B Sa 14 1744 del T 571 Frame shift, 15 novel amino acids then truncation Mother ϩ/- (ICP) Father ϩ/- 3 siblings ϩ/ϩ Absent ND P G 24 2975-2984 del Compound heterozygous 981 Frame shift in TMD 12, 3 novel amino acids then truncation Mother ϩ/ϩ Father ϩ/- ND 14.9 Bo S Bo N (sister of Bo S) 16 Nonsense 1938 C Ͼ T Q636X Linker region Truncation Mother ϩ/- Father ϩ/- 2 siblings ϩ/- Absent 2 ND B Aa 23 2901 C Ͼ T R957X TMD 11 Truncation Mother ϩ/- (ICP) Father ϩ/- 4 siblings ϩ/- or ϩ/ϩ Absent ND S F 10 Missense 1069 G Ͼ T S346I Serine to isoleucine in TMD6 Mother ϩ/- Father ϩ/- Faint 1 B H 11 1216 A Ͼ G E395G Glutamate to glycine between TMD 6 and first Walker A motif ND ND ND N I 14 1653 A Ͼ T I541F Isoleucine to phenylalanine in first Walker B motif Mother ϩ/- Father ϩ/- Absent ND M M 14 1699 T Ͼ G L556R Leucine to arginine in first Walker B motif ND ND ND P G 24 2979 G Ͼ A Compound heterozygous G983S Glycine to serine in TMD 12 Mother ϩ/- Father ϩ/ϩ ND 14.9 P A 6 Heterozygous Missense 444 T Ͼ C W138R Trytophan to arginine in TMD 2 Mother ϩ/- Father ϩ/ϩ ND 6.7 M Aa 12 1302 A Ͼ G T424A Threonine to alanine in first Walker A motif ND gallbladder lithiasis in father Faint 6.3 P K 12 1307 G Ͼ A V425M Valine to methionine in first Walker A motif ND Normal ND G A 14 1723 A Ͼ G D564G Aspartate to glycine in first Walker B motif ND ND ND G M 17 2132 T Ͼ C F711S Phenylalanine to serine in TMD 7 ND ND ND L M 16 Polymorphism 1986 A Ͼ G Homozygous R652G Arginine to glycine in linker region Mother ϩ/- (suspicion of ICP) Father ϩ/- ND ND Ga M " Heterozygous " " Mother ϩ/- Father ϩ/ϩ 1 sibling ϩ/- ND 9.7 L H L F (sister of L H) " Heterozygous " " ND ND ND VH C " Heterozygous " " Mother ϩ/ϩ Father ϩ/- ND ND NOTE. Login to comment 152 ABCB4 p.Arg652Gly plantation so far. Among these 7 patients, 5 have the R652G polymorphism. Login to comment 171 ABCB4 p.Arg652Gly An additional missense mutation (R652G) was located in the linker region. Login to comment 172 ABCB4 p.Arg652Gly Although it is a nonconservative mutation, it was found heterozygous in control chromosomes with the same frequency, and this excludes the possibility that R652G, by itself, can cause clinical symptoms. Login to comment 174 ABCB4 p.Arg652Gly One possibility is that the R652G mutation has mild consequences, explaining the favorable outcome of patients with this mutation under UDCA therapy, but combined with another mutation or in circumstances such as pregnancy leads to clinical symptoms. Login to comment