ABCMdb

PMID: 10811882

Ringpfeil F, Lebwohl MG, Christiano AM, Uitto J
Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter.
Proc Natl Acad Sci U S A. 2000 May 23;97(11):6001-6., 2000-05-23 [PubMed]

Sentences

No. Mutations Sentence Comment

59 ABCC1 p.Gly671Val NM004996) revealed a neutral polymorphism (2031G3C; V677V) in one PXE family (family 4 in Fig. 1), and a heterozygous glycine-to-valine polymorphism (2012G3T; G671V) in another (family 2 in Fig. 1). Login to comment 74 ABCC6 p.Arg1141* The mutation in exon 24 resulted in substitution of a codon for arginine by a stop codon, a mutation designated R1141X. Login to comment 75 ABCC6 p.Arg1268Gln The mutation in exon 27 resulted in substitution of a codon for arginine by a codon for glutamine (R1268Q). Login to comment 77 ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1268Gln ABCC6 p.Arg1268Gln ABCC6 p.Arg1268Gln ABCC6 p.Arg1138Gln ABCC6 p.Arg1138Trp MRP6 mutations in families with PXE Family Age and sex of proband Mutation Exon Consequence Verification* 1 53 F 3421C 3 T 24 R1141X BsiYI 3803G 3 A 27 R1268Q BstXI 2 29 F 3412C 3 T 24 R1138W MspI 3 40 F 3421C 3 T 24 R1141X BsiYI Partial deletion 24† Allelic loss D16S2720 MRP6 D16B9622 4 53 F 3736-1G 3 A 27 Altered splicing of exon 27 AciI Partial deletion 27† Allelic loss D16S2720 MRP6 D16B9622 5 60 M 3413G 3 A 24 R1138Q MspI 3803G 3 A 27 R1268Q BstXI 6 28 F 3421C 3 T 24 R1141X BsiYI 7 41 M 3803G 3 A 27 R1268Q BstXI 8 25 F 3421C 3 T 24 R1141X BsiYI *Mutations were verified in the proband and his/her family members by digestion with restriction enzyme, or in case of deletion, by microsatellite markers indicated. Login to comment 89 ABCC6 p.Arg1138Trp This substitution resulted in the replacement of an arginine codon by a codon for tryptophan (R1138W). Login to comment 90 ABCC6 p.Arg1138Trp This nucleotide substitution abolished a restriction site for MspI, and evaluation of the rest of the family by MspI digestion revealed that the mother of the proband was also homozygous for the mutation R1138W. Login to comment 93 ABCC6 p.Arg1138Trp Examination of the proband`s father (V-2) also revealed the mutation R1138W in the heterozygous state. Login to comment 98 ABCC6 p.Arg1141* Examination of the proband`s DNA by CSGE and nucleotide sequencing (Fig. 2 A and B) revealed a homozygous mutation in exon 24, 3421C3T, which resulted in a premature termination codon R1141X. Login to comment 101 ABCC6 p.Arg1141* Examination of the parents revealed that the father (I-2) was heterozygous for the mutation R1141X. Login to comment 111 ABCC6 p.Arg1141* These findings are consistent with the interpretation that the proband and her sister had inherited a nonsense mutation from the father and a deletion mutation affecting exon 24 of MRP6 from the mother, thus reducing the paternal mutation R1141X to hemizygosity. Login to comment 113 ABCC6 p.Arg1141* A search for other mutations in the MRP6 gene was unyielding, and he may therefore manifest with mild features of PXE, reflecting his carrier status for the mutation R1141X. Login to comment 142 ABCC6 p.Arg1141* ABCC6 p.Arg1268Gln ABCC6 p.Arg1268Gln ABCC6 p.Arg1138Gln Evaluation of their DNA revealed that the patient in family 5 was compound heterozygous for nucleotide substitutions 3413G3A and 3803G3A in exons 24 and 27, which resulted in the amino acid substitutions R1138Q and R1268Q, respectively. In families 6-8, heterozygous nucleotide substitutions were discovered, resulting in the mutations R1141X (families 6 and 8), and R1268Q (family 7). Login to comment 150 ABCC6 p.Arg1138Trp Affected individuals in one of the families showed a homozygous missense mutation (family 2: R1138W), whereas those in another family were compound heterozygous for a nonsense mutation and a missense mutation (family 1: R1141X͞R1268Q). Login to comment 159 ABCC6 p.Arg1141* ABCC6 p.Arg1268Gln Although only one mutation in each of the latter three individuals was observed, it is likely that PXE in these cases was also autosomal recessive, because each of the two distinct mutations (R1141X and R1268Q) discovered in these three probands were also present in the multiplex families, and the heterozygous carriers did not show definitive signs of the disease. Login to comment