ABCMdb

PMID: 16854481

Kiec-Wilk B, Surdacki A, Dembinska-Kiec A, Michalowska J, Stachura-Deren M, Dubiel JS, Dudek D, Rakowski T, Szastak G, Bodzioch M, Aslanidis C, Schmitz G
Acute myocardial infarction and a new ABCC6 mutation in a 16-year-old boy with pseudoxanthoma elasticum.
Int J Cardiol. 2007 Mar 20;116(2):261-2. Epub 2006 Jul 18., 2007-03-20 [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCC6 p.Arg1141* ABCC6 p.Arg1221His A 16-year-old survivor of acute myocardial infarction with 3-vessel coronary artery disease exhibited compound heterozygosity for the well-known nonsense mutation (c.3421C>T; R1141X) in exon 24 and a novel missense mutation (c.3662G>A; R1221H) in exon 26 of the ABCC6 gene. Login to comment 8 ABCC6 p.Arg1141* Interestingly, the most common disease-causing mutation in the European population (c.3421C>T; R1141X) predisposes to premature coronary artery disease in the absence of even mild ocular or dermatological PXE signs [4], whereas in PXE subjects abnormalities within the skin and eyes usually predominate and coronary symptoms are relatively rare generally occurring after the age of 35 [5]. Login to comment 22 ABCC6 p.Arg1141* ABCC6 p.Arg1221His The PXE boy exhibited compound heterozygosity for the well-recognized mutation (c.3421C>T; R1141X) in exon 24, and a novel one (c.3662G>A; R1221H) in exon 26 (Fig. 2). Login to comment 24 ABCC6 p.Arg1268Gln The patient was also a heterozygous carrier of a neutral polymorphism (c.3803G>A; R1268Q) in exon 27 [2] (Fig. 3). Login to comment 25 ABCC6 p.Arg1141* That a heterozygous form of the common R1141X nonsense mutation in exon 24 appears insufficient for the appearance of PXE, confirms earlier observations [5]. Login to comment 26 ABCC6 p.Arg1141* ABCC6 p.Arg1221His We suggest that the coincidence of the heterozygous R1141X mutation and a novel one (c.3662G>A; R1221H) in exon 26 on the other allele might have been responsible for PXE in the presented case. Login to comment 27 ABCC6 p.Arg1221Cys Additionally, the previously described PXE-causing missense mutations in exon 26 also affected the evolutionary conserved (http://www.ncbi.nlm.nih.gov/ BLAST) arginine residue in position 1221 (R1221C) [3,5,6]. Login to comment 28 ABCC6 p.Arg1221Cys Interestingly, one of these subjects (c.3661C>T; R1221C) was a 23-year-old PXE woman with 2-vessel coronary artery disease in addition to ocular and dermatological involvement [6], i.e. similar to our patient. Login to comment