ABCMdb

PMID: 10922396

Teder M, Klaassen T, Oitmaa E, Kaasik K, Metspalu A
Distribution of CFTR gene mutations in cystic fibrosis patients from Estonia.
J Med Genet. 2000 Aug;37(8):E16., [PubMed]

Sentences

No. Mutations Sentence Comment

7 ABCC7 p.Gly551Asp ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Leu206Trp First, several known mutations were tested directly by the heteroduplex analysis (HA; F508, 394delTT, polyT variants in IVS8), restriction digestion (RD; G551D, R553X, 1811+1.6kbA→G, L206W, 3849+10kbC→T), and amplification refractory mutation system (ARMS, kits from Cellmark Diagnostics, UK; G542X, 621+1G→T, N1303K). Login to comment 12 ABCC7 p.Ser1235Arg Each of these mutations was detected once, except for S1235R, which was found in two heterozygotes. Login to comment 19 ABCC7 p.Ile1005Arg ABCC7 p.Arg117Cys ABCC7 p.Lys1200Glu To scan for several known mutations simultaneously, a multiple allele specific primer extension (MASPE) method was developed.23 Thirty eight mutations were chosen: 30 of the most common mutations world wide24 and eight mutations of regional interest (394delTT, 3821delT, 2143delT, 2184insA, 3732delA/K1200E, R117C, and I1005R), previously detected in Scandinavia,2 Russia,25 or Germany.19 Fifteen target exons were amplified to get the templates for primer extension.26 Owing to the dense location of the mutation sites in seven exons, both DNA strands were used as templates to avoid overlapping of the extension primers. Login to comment 26 ABCC7 p.Ser1235Arg ABCC7 p.Ser1235Arg ABCC7 p.Ile1005Arg ABCC7 p.Ile1005Arg ABCC7 p.Ser1196* ABCC7 p.Ser1196* ABCC7 p.Arg1066His ABCC7 p.Arg1066His ABCC7 p.Glu217Gly ABCC7 p.Glu217Gly The mixture was heated to 80°C, Table 1 Mutations identified in CF patients from Estonia Mutation Exon No of chromosomes Frequency (%) Method Reference F508 10 31 51.7 HA 6 394delTT 3 8 13.3 HA 7 359insT 3 1 SSCP 16 3659delC 19 1 SSCP 17 E217G 6a 1 DGGE 18 H117C 4 1 SSCP 19 I1005R 17a 1 SSCP 19 R1066H 17b 1 DGGE 20 S1196X 19 1 DGGE 21 S1235R 19 2 DGGE 22 Unidentified 12 Total 60 Table 2 Genotypes of the 30 CF patients from Estonia No of patients Genotype 8 F508/ F508 6 F508/394delTT 1 F508/I1005R 1 F508/359insT 1 F508/3659delC 1 F508/H117C 1 F508/R1066H 1 F508/S1196X 1 394delTT/394delTT 2 S1235R/U* 3 F508/U 1 E217G/U 3 U/U *Unidentified mutation Electronic letter of 4 www.jmedgenet.com cooled slowly to 30°C, and then divided into four sets of 60 µl. Login to comment 61 ABCC7 p.Ile1005Arg ABCC7 p.Ser1196* S1196X was associated with haplotype D-16-7-17, the same in our population and in Russia.21 Haplotype A-17-32-13 was determined for mutation I1005R. Login to comment 62 ABCC7 p.Arg117Cys ABCC7 p.Arg1066His It diVers from the one found in Germany by one repeat in the IVS8 locus and could have been derived from it by slippage mechanism.31 The mutations R117C and R1066H are obviously recurrent and therefore neither diallelic markers nor microsatellites matched to the corresponding haplotypes from the other populations. Login to comment 66 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* This is the second most frequent mutation in several Nordic populations, with a relative frequency of 1.9% in Denmark,2 3.2% in Flanders,32 6.5% in Sweden,2 2.2-5.5% in Norway,2 and 30% in Finland.3 It was also found on 1.5% of the CF chromosomes in Russia.32 We did not find any of the mutations more common in European populations, such as G542X (2.6%), N1303K (1.6%), G551D (1.5%), or W1282X (1.0%),4 which is not surprising, as the relative frequency of these mutations is less than 1% in Nordic countries also. Login to comment