ABCC6 p.Gly207Arg
| LOVD-ABCC6: |
p.Gly207Arg
D
|
| Predicted by SNAP2: | A: D (66%), C: D (85%), D: D (80%), E: D (71%), F: D (91%), H: D (75%), I: D (85%), K: D (75%), L: D (85%), M: D (85%), N: D (75%), P: D (91%), Q: D (66%), R: D (59%), S: D (53%), T: D (71%), V: D (80%), W: D (95%), Y: D (91%), |
| Predicted by PROVEAN: | A: N, C: D, D: N, E: N, F: D, H: N, I: D, K: N, L: D, M: D, N: N, P: D, Q: N, R: N, S: N, T: N, V: D, W: D, Y: D, |
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[hide] A spectrum of ABCC6 mutations is responsible for p... Am J Hum Genet. 2001 Oct;69(4):749-64. Epub 2001 Aug 31. Le Saux O, Beck K, Sachsinger C, Silvestri C, Treiber C, Goring HH, Johnson EW, De Paepe A, Pope FM, Pasquali-Ronchetti I, Bercovitch L, Marais AS, Viljoen DL, Terry SF, Boyd CD
A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum.
Am J Hum Genet. 2001 Oct;69(4):749-64. Epub 2001 Aug 31., [PMID:11536079]
Abstract [show]
To better understand the pathogenetics of pseudoxanthoma elasticum (PXE), we performed a mutational analysis of ATP-binding cassette subfamily C member 6 (ABCC6) in 122 unrelated patients with PXE, the largest cohort of patients yet studied. Thirty-six mutations were characterized, and, among these, 28 were novel variants (for a total of 43 PXE mutations known to date). Twenty-one alleles were missense variants, six were small insertions or deletions, five were nonsense, two were alleles likely to result in aberrant mRNA splicing, and two were large deletions involving ABCC6. Although most mutations appeared to be unique variants, two disease-causing alleles occurred frequently in apparently unrelated individuals. R1141X was found in our patient cohort at a frequency of 18.8% and was preponderant in European patients. ABCC6del23-29 occurred at a frequency of 12.9% and was prevalent in patients from the United States. These results suggested that R1141X and ABCC6del23-29 might have been derived regionally from founder alleles. Putative disease-causing mutations were identified in approximately 64% of the 244 chromosomes studied, and 85.2% of the 122 patients were found to have at least one disease-causing allele. Our results suggest that a fraction of the undetected mutant alleles could be either genomic rearrangements or mutations occurring in noncoding regions of the ABCC6 gene. The distribution pattern of ABCC6 mutations revealed a cluster of disease-causing variants within exons encoding a large C-terminal cytoplasmic loop and in the C-terminal nucleotide-binding domain (NBD2). We discuss the potential structural and functional significance of this mutation pattern within the context of the complex relationship between the PXE phenotype and the function of ABCC6.
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No. Sentence Comment
129 Premature termination mutations frequently result in the nonsense-mediated decay (NMD) of mutant mRNA products and significantly reduce mutant transcript levels (Maquat 1996; Nagy and Table 3 Missense Neutral Variants Identified in the ABCC6 Gene in a Cohort of 122 Patients CHANGE IN STATUS a ORIGIN(S)b EXON(S) NO. OF ALLELES/ PXE CHROMOSOMES NO. OF ALLELES/ CONTROL CHROMOSOMES c Amino Acid Nucleotide G61D 182GrA ht SA 2 1/244 0/200 G207R 619GrA ht Belgium 6 1/244 0/200 R265G 793ArG ht Belgium 7 1/244 0/200 K281Ed 841ArG ht, hm SA 8 5/8d Nd I319Vd 955ArG ht, hm SA 8 5/8d Nd N497K 1489CrA ht Belgium 12 1/244 0/200 V614A 1841TrC ht, hm All 14 200/244 163/200 H632Qd 1896CrA ht, hm SA, Belgium 15 17/24d Nd L953H 2858TrA ht US 22 1/244 0/200 W1241C 3723GrC ht Germany 26 1/244 0/200 R1268Q 3803GrA ht All 27 23/244 31/200 a ht p heterozygote; hm p homozygote.
X
ABCC6 p.Gly207Arg 11536079:129:440
status: NEW