ABCMdb

PMID: 11439001

Meloni I, Rubegni P, De Aloe G, Bruttini M, Pianigiani E, Cusano R, Seri M, Mondillo S, Federico A, Bardelli AM, Andreassi L, Fimiani M, Renieri A
Pseudoxanthoma elasticum: Point mutations in the ABCC6 gene and a large deletion including also ABCC1 and MYH11.
Hum Mutat. 2001;18(1):85., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCC6 p.Arg1164* ABCC6 p.Tyr227* ABCC6 p.Arg518* Mutation analysis on the other allele of the family, as well as on two additional sporadic cases, revealed nonsense (Y227X, R518X, R1164X) and frame-shift (c.960delC) mutations in ABCC6 (MRP6) further confirming the role of this multi-drug resistance gene in the etiology of pseudoxanthoma elasticum. Login to comment 8 ABCC6 p.Val614Ala In the course of the analysis five nonpathogenic variants were found in ABCC6: 1233T>C, 1245G>A, 1838 T>G (V614A), 1890C>G, and 3506+83C>A. Login to comment 57 ABCC6 p.Arg1164* ABCC6 p.Arg518* Two of them (R518X and R1164X) are C to T transitions in a CpG dinucleotide causing a substitution of arginine (CGA) with a stop codon (TGA); they were identified in exon 12 and exon 24 in the two sporadic cases in the heterozygous state (patients 11 and 12). Login to comment 59 ABCC6 p.Tyr227* In patient 11 we identified a second mutation (Y227X) which is a C to G transversion in exon 7 leading to the substitution of a tyrosine (TAC) with a stop codon (TAG). Login to comment 72 ABCC6 p.Tyr227* NH2 COOHR1164XR518X 960delC Y227X A B DISCUSSION Linkage analysis of a large Italian PXE family led to the detection of a submicroscopic deletion by hemizygosity of marker D16S405, allowing us to define a critical region containing three genes: MYH11, ABCC1 and ABCC6. Login to comment 95 ABCC6 p.Arg1164* ABCC6 p.Tyr227* ABCC6 p.Arg518* ABCC6 p.Val614Ala Mutations and variants in ABCC6 nt change Mutations 681 C ->G 960delC 1552 C ->T 3490 C ->T Non pathogenic variants 1233 T ->C 1245 G ->A 1838 T->G 1890 C->G c.3506+83 C ->A protein change Y227X frame-shift from I320 R518X R1164X N411N N415N V614A T630T _ exon 7 11 exon 8 family exon 12 11 exon 24 12 exon 10 11 exon 10 11 exon 14 11, 12 exon patient 11 11 12 exon 14 exon 24 11 11, 12 11, 12 Re-evaluation of the phenotype in the family with the large deletion did not reveal significant additional manifestations, suggesting that heterozygous ABCC1 and MYH11 deletion does not give rise to an obvious phenotype. Login to comment