ABCMdb

PMID: 18800149

Li Q, Grange DK, Armstrong NL, Whelan AJ, Hurley MY, Rishavy MA, Hallgren KW, Berkner KL, Schurgers LJ, Jiang Q, Uitto J
Mutations in the GGCX and ABCC6 genes in a family with pseudoxanthoma elasticum-like phenotypes.
J Invest Dermatol. 2009 Mar;129(3):553-63. Epub 2008 Sep 18., [PubMed]

Sentences

No. Mutations Sentence Comment

3 ABCC6 p.Arg1141* The proband`s mother and aunt, also manifesting with PXE-like skin changes, were heterozygous carriers of a missense mutation (p.V255M) in GGCX and a null mutation (p.R1141X) in the ABCC6 gene, suggesting digenic nature of their skin findings. Login to comment 31 ABCC6 p.Arg1141* ABCC6 p.Arg1141* Patient (III-3) Patient (III-3) Patient (III-3) Patient (II-2) Patient (II-3) Patient (II-3) a b c d e f g Skin Coagulation GGCX ABCC6 GGCX ABCC6 V255M S300F R1141X V255M S300F R1141X 1 1 2 3 4 3 2 21 5 II I III - -+ + + - - - - + + + + + + + + + Figure 1. Login to comment 41 ABCC6 p.Arg1141* The recurrent mutation, p.R1141X, which is particularly prevalent (about 30% of all detected mutations in PXE patients of the European extraction; Pfendner et al., 2007) was found in the DNA from the father, mother, the maternal aunt and the younger brother, but not in the proband herself or her sister (Figures 1g and 3a). Login to comment 64 ABCC6 p.Arg1141* The latter individuals were also carriers of the ABCC6 nonsense mutation p.R1141X. Login to comment 65 ABCC6 p.Arg1141* Specifically, the mother and her twin sister were heterozygous for the GGCX missense mutation p.V255M and the ABCC6 nonsense mutation p.R1141X, suggesting digenic inheritance of their cutaneous findings. Login to comment 66 ABCC6 p.Arg1141* However, the proband`s younger brother and father were heterozygous carriers of the p.S300F mutation in the GGCX gene although they also carried the p.R1141X mutation in the ABCC6 gene; they did not display any signs of cutaneous findings or hematologic disorder. Login to comment 67 ABCC6 p.Arg1141* Assay of c-glutamyl carboxylase activity Previous studies have clearly demonstrated that the p.R1141X mutation in the ABCC6 gene in heterozygous carriers does not cause PXE (Wegman et al., 2005; Pfendner et al., 2007). Login to comment 77 ABCC6 p.Arg1141* (a) Identification of the recurrent nonsense mutation p.R1141X in the ABCC6 gene. Login to comment 131 ABCC6 p.Arg1141* The recurrent mutation p.R1141X was found in the DNA from the father, mother, the maternal aunt and the younger brother, but not in the proband herself or her sister. Login to comment 140 ABCC6 p.Arg1141* The latter individuals were also carriers of the ABCC6 nonsense mutation p.R1141X. Login to comment 141 ABCC6 p.Arg1141* It should be noted that the mother and her twin sister were heterozygous for one of the GGCX missense mutation p.V255M and one ABCC6 nonsense mutation p.R1141X, suggesting digenic inheritance of their cutaneous findings. Login to comment 144 ABCC6 p.Arg1141* It should be noted, however, that in a cohort of 4300 families with PXE analyzed in our laboratory for mutations in the ABCC6 gene, five individuals were heterozygous carriers of a mutation (p.R1141X) in one ABCC6 allele only, yet none of them carried a mutation in the GGCX gene (unpublished). Login to comment 163 ABCC6 p.Arg1141* Mutations in the ABCC6 gene have been shown to cause PXE, an autosomal recessive disorder (Ringpfeil et al., 2006), but heterozygous carriers of mutations, such as p.R1141X detected in the proband`s mother and aunt, are asymptomatic (Wegman et al., 2005; Pfendner et al., 2007). Login to comment 170 ABCC6 p.Arg1141* These two individuals were heterozygous carriers of p.R1141X mutation in ABCC6 and p.V255M in GGCX. Login to comment 171 ABCC6 p.Arg1141* As heterozygous carriers of p.R1141X in ABCC6 alone do not manifest PXE and GGCX mutations with respect to coagulation disorder are recessive, these findings suggest that the skin phenotype in these two individuals may be because of digenic inheritance. Login to comment 173 ABCC6 p.Arg1141* The reasons for the fact that the proband`s father and her brother were heterozygous carriers of mutations in the ABCC6 gene (p.R1141X) and the GGCX gene (p.S300F) yet did not display any cutaneous findings are not clear. Login to comment