ABCMdb

PMID: 1709778

Devoto M, Ronchetto P, Fanen P, Orriols JJ, Romeo G, Goossens M, Ferrari M, Magnani C, Seia M, Cremonesi L
Screening for non-delta F508 mutations in five exons of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in Italy.
Am J Hum Genet. 1991 Jun;48(6):1127-32., [PubMed]

Sentences

No. Mutations Sentence Comment

27 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly542* In addition, a variable number of the same chromosomes had been previously tested, with other methods (ASO and/or digestion with restriction enzymes as described below), for the presence of other known mutations-in particular, 91 for G542X (Kerem et al. 1990), 56 for W1282X (Vidaud et al. 1990), and 96 for R553X (Cutting et al. 1990b). Login to comment 28 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly542* For DGGE screening, a first group of 61 chromosomes originated from a corresponding number of com- poundheterozygous patients who carried an identified mutation (57 deltaF508, two W1282X, one G542X, andone R553X) on one oftheirtwo CFchromosomes. Login to comment 32 ABCC7 p.Gly542* Screening for CFTR gene mutations already published or known through the CF Genetic Analysis Consortium was carried out on random samples of CF chromosomes by PCR amplification ofspecific exons that was followed by digestion with restriction enzymes indicated in table 2 which recognize mutation sites inside the amplification product and, in one case (G542X), by hybridization with the allele-specific oligonucleotides (ASO). Login to comment 34 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Gly542* ABCC7 p.Ser549Asn ABCC7 p.Ser1255* Table 2 Results of Screening for Known Mutations Total No. of No. of Chromosomes Chromosomes Overall Mutation Exon Method With the Mutationa Screenedb Frequencyc Reference R334W......... 7 MspI 2 198 1.01 X. Estivill, personal communication R347P......... 7 HhaI or NcoI 4 183 2.19 Dean et al. 1990 G542X ......... 11 ASO (DGGE) 15 (4) 176 (18) 9.79 Kerem et al. 1990 S549N......... 11 DdeI 1 159 .63 Cutting et al. 1990b G5S1D ......... 11 HincII or MboI 0 186 Cutting et al. 1990b R553X ......... 11 HincIl (DGGE) 5 (1) 186 (13) 3.02 Cutting et al. 1990b 1717-1G-A .... 11 (DGGE) (12) (109) 11.01 Guillermit et al. 1990 S1255X ......... 20 HindIII 0 130 Cutting et al. 1990a W1282X......... 20 MnlI (DGGE) 7 (3) 124 (53) 5.65 Vidaud et al. 1990 a Numbers in parentheses are number of mutations found through DGGE. Login to comment 44 ABCC7 p.Gln552* The second mutation (Q552X) located in exon 11 is a C-to-T transition at position 1786 which causes the substitution of a glutamine residue in position 552 by a stop codon. Login to comment 48 ABCC7 p.Arg553* The first (2909delT) is a frameshift mutation Table 3 New Mutations Detected by DGGE Analysis and Direct Sequencing HAPLOTYPE MUTATION MetD MetH MetH E6 W3D14 PT3 XV2c CS7 KM19 E9 E4.1 J3.11 ON OTHER REGIONAL MUTATION TaqI MspI TaqI TaqI HindIII BanII TaqI HhaI PstI MspI MspI MspI CHROMOSOME PHENOTYPEa ORIGIN Exon 11: 1784delG ...1 .... ..... ... ... 2 ... 1 1 ... 2 R553X PI Lombardia 1784delG. Login to comment 49 ABCC7 p.Gly1244Glu .. 2 ... ... 2 ... 1 1 ... 2 Unknown PI Lombardia QS52X.. ... 1 1 2 2 1 2 1 2 2 1 Unknown PI Ven~to Exon 15: 2909delT ...1... ...... ... ... 1 1 ... 2 Unknown PI Lombardia Exon 20: G1244E .....1 2 2 1 2 2 1 1 1 1 ... 1 deltaF508 PI Sicily a PI = pancreatic insufficiency. Login to comment 52 ABCC7 p.Gly1244Glu The mutation found in exon 20 is a missense mutation due to a G-to-A transition at position 3863 and generates a glycine-to-glutamic-acid substitution in codon 1244 (G1244E). Login to comment 57 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly542* In this way, a total of four G542X, one R553X, and 12 1717-1G--oA in exon 11 and of three W1282X in exon 20 could be identified (see table 2). Login to comment 82 ABCC7 p.Gln552* However, there is little doubt that Q552X, 1784delG, and 2909delT are disease-causing mutations, since all of them cause a premature termination of CFTR synthesis. Login to comment 83 ABCC7 p.Gly1244Glu As for G1244E, it seems that the substitution of a charged amino acid (glutamic acid) for a neutral one (glycine) may be relevant to the protein functioning. Login to comment