ABCMdb

PMID: 20491760

Li Q, Torok L, Kocsis L, Uitto J
Mutation analysis (ABCC6) in a family with pseudoxanthoma elasticum: presymptomatic testing with prognostic implications.
Br J Dermatol. 2010 Sep;163(3):641-3. doi: 10.1111/j.1365-2133.2010.09856.x. Epub 2010 May 11., [PubMed]

Sentences

No. Mutations Sentence Comment

17 ABCC6 p.Arg1268Gln ABCC6 p.Arg1221His The analysis of the ABCC6 gene was performed by polymerase chain reaction amplification of all exons and flanking intronic sequences, followed by automated nucleotide sequencing, as described previously.2 Two homozygous sequence variants were identified in the ABCC6 gene of the proband: p.R1221H and p.R1268Q. Login to comment 20 ABCC6 p.Arg1221His Previously, p.R1221H has been identified as a pathogenic mutation in a patient with PXE.6 Furthermore, the arginine in the position 1221 is evolutionarily highly conserved (Fig. Login to comment 22 ABCC6 p.Arg1268Gln ABCC6 p.Arg1221His In contrast, the p.R1268Q sequence variant has been suggested to be a relatively common polymorphism with an allelic frequency of ~30% in healthy Caucasian and Japanese populations.7,8 Collectively, it appears that p.R1221H is the pathogenic mutation resulting in PXE, when present in both alleles, as in the case of the proband of this study. Login to comment 32 ABCC6 p.Arg1221His (b) Sequencing of the proband`s ABCC6 gene revealed that the arginine in position 1221 in control DNA is replaced by homozygous substitution by histidine (p.R1221H) reflecting G-to-A nucleotide substitution (arrow) and confirming the diagnosis of PXE. Login to comment 33 ABCC6 p.Arg1221His The 13-year old younger brother (II-3) is a heterozygous carrier of the p.R1221H substitution and is consequently predicted not to develop PXE, similar to his parents. Login to comment 34 ABCC6 p.Arg1268Gln ABCC6 p.Arg1221His The mutation p.R1221H cosegregates in the family with an allelic polymorphism, p.R1268Q (a). Login to comment 51 ABCC6 p.Arg1268Gln 7 Germain DP, Perdu J, Remones V, Jeunemaitre X. Homozygosity for the R1268Q mutation in MRP6, the pseudoxanthoma elasticum gene, is not disease-causing. Login to comment 55 ABCC6 p.Arg1141* 9 Trip MD, Smulders YM, Wegman JJ et al. Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong increase in the prevalence of coronary artery disease. Login to comment 57 ABCC6 p.Arg1141* 10 Ko¨blo¨s G, Andrikovics H, Proha´szka Z et al. The R1141X loss-of- function mutation of the ABCC6 gene is a strong genetic risk factor for coronary artery disease. Login to comment