ABCMdb

PMID: 7516305

Audrezet MP, Canki-Klain N, Mercier B, Bracar D, Verlingue C, Ferec C
Identification of three novel mutations (457 TAT-->G, D192G, Q685X) in the Slovenian CF patients.
Hum Genet. 1994 Jun;93(6):659-62., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCC7 p.Gln685* ABCC7 p.Asp192Gly As a result of this survey 84% of the alleles are now clearly identified and we describe in this paper three novel mutations (457 TAT-->G, D192G, and Q685X). Login to comment 31 ABCC7 p.Gln685* The other 38, carrying an unidentified mutated allele, were selected for DGGE screening in the 27 exons of the CFTR gene, using the conditions and primers we have defined C T A G G A T C Q685X 457 TAT -~ G Fig. 1. Login to comment 32 ABCC7 p.Gln685* The Q685X (left) and the 457 TAT---~G(right) mutations. Login to comment 40 ABCC7 p.Gly542* She carries the G542X mutation on the other chromosome (Table 1, CF-53). Login to comment 41 ABCC7 p.Asp192Gly D192G The nucleotide variation is A---~Gat position 706 in exon 5, which leads to a glycine instead of an aspartic acid at codon 192. Login to comment 45 ABCC7 p.Gln685* The nucleotide changes is a C--->T at position 2185, leading to a stop codon (Q685X). Login to comment 47 ABCC7 p.Gln685* The complete genotype is AF508/Q685X (Table 1, CF-52). Login to comment 50 ABCC7 p.Gly542* ABCC7 p.Gln685* ABCC7 p.Asp192Gly Some clinical data of patients with the three novel mutations Patient Exon Mutation Age of Age at Chloride sweat Pancreatic Lung Pseudomonas onset diagnostic test mmol/per 1 function disease aeruginosa CF-53 4 457 TAT--~G Birth 4 months 90.9-167.0 Insufficient Severe Yes 11 G542X CF-67 5 D192G 2 months 3 months 58.8-106.7 Insufficient Moderate No 10 AF508 CF-52 13 Q685X 3 months 6 years 113.4-177.2 Insufficient Severe Yes 10 AF508 Table 2. Login to comment 51 ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Ile148Thr ABCC7 p.Gln552* ABCC7 p.Arg1066His ABCC7 p.Gln685* ABCC7 p.Asp192Gly Mutations identified in the population of Slovenia Number of chromosomes Mutations 661 83 AF508 4 G542X 5 R1162X 2 3905 ins T 2 I148T 1 Q552X 1 Q685X 1 S4X 1 457 TAT---~G 1 D192G 1 R1066H 19 Unidentified 121 Exons Frequencies References 10 68.60% Kerem et al. (1989) 11 3.30% Kerem et al. (1990) 19 4.10% Gasparini et al. (1991) 20 1.65% Personal Communication 4 1.65% Personal Communication 11 0.85% Devoto et al. (1991) 13 0.85% This study 1 0.85% Glavac et al. (1993) 4 0.85% This study and Glavac et al. (1993) 5 0.85% This study 17b 0.85% Ftrec et al. (1992) 15.70% by 11 mutations, occurring in 9 exons of the gene (1, 4, 5, 10, 11, 13, 17b, 19, and 20). Login to comment 54 ABCC7 p.Gly542* A study performed by Dabovic et al. (1992) in a cohort of 54 families, each with one living CF child, from Serbia, Montenegro, Bosnia, and Herzegovina showed that the AF508 accounts for 70% (76/108 CF chromosomes) of CFTR genes and the G542X, for 4% (4/108). Login to comment 63 ABCC7 p.Gly542* ABCC7 p.Arg1162* The distribution of mutations in our study differs from that observed in other populations of the Mediterranean area where, besides the AF508, two mutations, G542X and R1162X, have a frequency greater than 1% (Nunes et al. 1991). Login to comment 66 ABCC7 p.Gln685* ABCC7 p.Asp192Gly Of the three novel mutations reported here (Q685X, D192G, and 457TAT---~G), two are clearly pathogenic alleles. Login to comment 67 ABCC7 p.Gln685* Q685X corresponds to the creation of a stop codon, and 457TAT---)G is a deletion/insertion resulting in a frameshift mutation. Login to comment 68 ABCC7 p.Asp192Gly D192G is a missense mutation located in the transmembrane domain of the CFTR, changing a glycine for an aspartic acid. Login to comment 74 ABCC7 p.Gln685* Two of these novel alleles (Q685X and 457 TAT---~G) belong to class 1, i.e., they lead to defective protein production. Login to comment 76 ABCC7 p.Asp192Gly The third mutation (D192G) belongs to class 4, leading probably to abnormal conduction. Login to comment