ABCMdb

PMID: 21167005

Larusso J, Ringpfeil F, Uitto J
Pseudoxanthoma elasticum: a streamlined, ethnicity-based mutation detection strategy.
Clin Transl Sci. 2010 Dec;3(6):295-8. doi: 10.1111/j.1752-8062.2010.00243.x., [PubMed]

Sentences

No. Mutations Sentence Comment

20 ABCC6 p.Arg1141* The frequent p.R1141X mutation was distributed widely across Europe, while deletion of exons 23-29 (del23-29) was encountered in Northern Europe and in Northern Mediterranean countries. Login to comment 21 ABCC6 p.Arg1138Trp p.R1138W may be a marker for French descent, evidenced by its presence also in French Canadians. Login to comment 23 ABCC6 p.Gln378* ABCC6 p.Arg1339Cys Two mutations seem to be present worldwide without evidence of a founder effect, p.Q378X and p.R1339C, suggesting the presence of mutational hotspots. Login to comment 42 ABCC6 p.Arg1141* ABCC6 p.Arg1138Trp ABCC6 p.Gln378* ABCC6 p.Arg1339Cys A total of eight recurrent mutations were distinguished in the cohort, including nonsense (p.Q378X and p.R1141X), missense (p.R1138W and p.R1339C), splice site (3736-1G/A, 2787 + 1G/T), frameshift (2542 delG), and multiexon deletion (del exon 23-29). Login to comment 43 ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* In our PXE cohort, the recurring nonsense mutation p.R1141X was present in all five ethnic groups, with the exception of Asian, representing 15.4% of French Canadian, 19.2% of Mediterranean, 20.5% of Northern European, and 36.4% of Scandinavian mutations; overall it occurred in 22.9% (32/140) of all the alleles examined. The high frequency of this mutation in the Mediterranean and Northern European population may be explained by a founder effect.18 The allele p.R1141X was found to share a common haplotype identical by descent in French19 and Italian patients.20 In three different studies examining German,21 Italian,20 and French PXE patients,19 R1141X was found to be the most frequent mutation. Login to comment 44 ABCC6 p.Arg1141* p.R1141X segregated in a compound heterozygous mode in 50% of French Canadians, 80% in Mediterranean, 75% in Northern Europeans, and in 33.3% of Scandinavians. Login to comment 46 ABCC6 p.Arg1141* The p.R1141X mutation can be detected by BsiYI restriction enzyme digestion and agarose gel electrophoresis, and confirmation can be attained by sequencing. Login to comment 50 ABCC6 p.Arg1138Trp In this exon a recurrent mutation, p.R1138W, occurred exclusively in 46.1% of French Canadians. Login to comment 52 ABCC6 p.Arg1138Gln ABCC6 p.Arg1164* ABCC6 p.Arg1164Gln Exon 24 also harbored other mutations (p.R1138Q, p.R1164X, and p.R1164Q) that did not appear to have a predilection for specific ethnicities. Login to comment 53 ABCC6 p.Gln378* ABCC6 p.Arg1339Cys Two additional core mutations established in Mediterraneans and Scandinavians were p.Q378X and p.R1339C. Login to comment 54 ABCC6 p.Arg1339Cys p.R1339C segregated exclusively in 11.5% of Mediterraneans and 9.1% of Scandinavians. Login to comment 55 ABCC6 p.Gln378* p.Q378X distributed in 3.8% of Mediterraneans and 9.1% of Scandinavians. Login to comment 56 ABCC6 p.Gln378* We did not identify p.Q378X in the French Canadian population, but it did appear in Northern Europeans (3.8%) and Asians (0.8%). Login to comment 62 ABCC6 p.Arg1221Cys ABCC6 p.Arg1357Trp Noji et al. also identified two novel missense mutations p.R1221C and p.R1357W in a Japanese patient with PXE. Login to comment 64 ABCC6 p.Arg1141* Analysis of mutations found in Japanese patients by Noji et al.,22 combined with our study, suggested that neither the nonsense mutation p.R1141X nor the large deletion ABCC6 del 23-29 are frequent in this ethnicity group. Login to comment 67 ABCC6 p.Ala766Asp ABCC6 p.Glu1400Lys In two patients of Greek and Turkish origin Chassaing et al.19 discovered two novel mutations, p.A766D in exon 18 and p.E1400K in exon 29. Login to comment 81 ABCC6 p.Gln378* ABCC6 p.Arg1339Cys p.R1339C appeared in Northern Europeans and Scandinavians, whereas p.Q378X was presentworldwide.Thesplicesitemutation2787+1G/Twasfound in French Canadians and Northern Europeans. Login to comment 83 ABCC6 p.Arg1141* 17, 23, and24), suggest future screening strategies that incorporate the patient`s ethnic background.Suchdiagnosticstrategyshouldbeespeciallyefficient for the European and Mediterranean populations in which a number of PXE mutations occur frequently (p.R1141X and del exons 23-29). Login to comment 90 ABCC6 p.Arg1339Cys Nevertheless, evidence for a founder effect has been previously reported in the Afrikaner population in South Africa, in which 53% of the PXE alleles harbored pathogenetic p.R1339C mutation.18 In summary, we have identified a set of recurrent mutations in theABCC6geneamongfivedifferentethnicgroups.Knowledgeof apatients`ethnicorigincanfacilitateanefficientscreeningstrategy. Login to comment