ABCMdb

PMID: 19054062

Li Q, Jiang Q, Pfendner E, Varadi A, Uitto J
Pseudoxanthoma elasticum: clinical phenotypes, molecular genetics and putative pathomechanisms.
Exp Dermatol. 2009 Jan;18(1):1-11. Epub 2008 Oct 22., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCC6 p.Arg1141* More recently, missense mutations in the GGCX gene, either in compound heterozygous state or digenic with a recurrent ABCC6 nonsense mutation (p.R1141X), have been identified in patients with PXE-like cutaneous findings and vitamin K-dependent coagulation factor deficiency. Login to comment 64 ABCC6 p.Arg1141* Two mutations are recurrent and of high frequency: First, the most common recurring mutation, particularly in Caucasian individuals, is p.R1141X in exon 24, with a prevalence of approximately 30% of all PXE mutations. Login to comment 67 ABCC6 p.Arg1141* Nevertheless, only approximately 10% of all patients in a recent large US and European study (21) were homozygous or compound heterozygous for p.R1141X and del23-29 mutations, indicating that approximately 90% of all individuals in these PXE populations will require further analysis to identify the second mutation or both mutations in the ABCC6 gene causing their disease. Login to comment 68 ABCC6 p.Arg1164* ABCC6 p.Arg518* ABCC6 p.Gln378* Identification of additional recurrent nonsense mutations (p.Q378X in exon 9, p.R518X in exon 12 and p.R1164X in exon 24) as well as clustering of the missense mutations to exons 24 and 28 corresponding to the NBFs that are critical for the ATP binding and hydrolysis have allowed the development of streamlined mutation detection strategies to facilitate identification of mutations in the ABCC6 gene with the overall detection rate of up to 99% (for review see reference 26). Login to comment 173 ABCC6 p.Arg1141* The analysis revealed the presence of a recurrent mutation, p.R1141X, in the peripheral blood DNA in several family members but not in the proband herself or in her sister (Fig. 5). Login to comment 174 ABCC6 p.Arg1141* These individuals were heterozygous for the p.R1141X mutation, and no other ABCC6 mutation could be disclosed in this family. Login to comment 178 ABCC6 p.Arg1141* In contrast, individuals who were heterozygous carriers of the ABCC6 nonsense mutation p.R1141X were also heterozygous carriers of one of the GGCX missense mutations. Login to comment 179 ABCC6 p.Arg1141* Specifically, the finding of the GGCX missense mutation p.V255M in combination of the ABCC6 nonsense mutation p.R1141X suggests the possibility of digenic inheritance of their cutaneous findings (59). Login to comment 184 ABCC6 p.Arg1141* Mutation analysis in the nuclear pedigree identified the presence of the p.R1141X nonsense mutation in the ABCC6 gene and two missense mutations, p.V255M and p.S300F, in the GGCX gene, as indicated on the left. Login to comment