ABCMdb

PMID: 7535742

Bonizzato A, Bisceglia L, Marigo C, Nicolis E, Bombieri C, Castellani C, Borgo G, Zelante L, Mastella G, Cabrini G, et al.
Analysis of the complete coding region of the CFTR gene in a cohort of CF patients from north-eastern Italy: identification of 90% of the mutations.
Hum Genet. 1995 Apr;95(4):397-402., [PubMed]

Sentences

No. Mutations Sentence Comment

3 ABCC7 p.Arg709* We identified 22 mutations, four of which are novel, viz. 711+5G--~A, R709X, 3132delTG and 2790-2A---~G, and we characterised 90.2% (203/225) of the CF chromosomes. Login to comment 5 ABCC7 p.Arg709* We confirm some previously reported genotype-phenotype correlations and we report a new nonsense mutation (R709X) associated with a pancreatic sufficient phenotype. Login to comment 35 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Gly85Glu ABCC7 p.Gln552* ABCC7 p.Arg709* Table 1 CF mutations identified in this cohort study (225 chromosomes from Veneto and Trentino Alto-Adige) n Number of CF chromosomes, Cum fi cumulative fraction, wnovel mutation identified during this study " Cystic Fibrosis Genetic Analysis Consortium, personal comunication Table 2 DNA sequence variations identified in this cohort study (w Novel sequence variation identified during this study a Cystic Fibrosis Genetic Analysis Consortium, personal comunication Mutation Exon n % Cure fr References AF508 l0 107 47.56 47.56 Kerem et al. 1989 R1162X 19 22 9.78 57.33 Gasparini et al. 1991 2183AA----~G 13 21 9.33 66.67 Bozon et al. 1994 N1303K 21 9 4.00 70.67 Osborne et al. t991 G542X 11 6 2.67 73.33 Kerem et al. 1990 711+5G--~A intron 5 6 2.67 76.00 w 1717 1G--~A intron 10 5 2.22 78.22 Kerem et al. 1990 G85E 3 3 1.33 79.56 Zielenski et al. 1991~' R553X 11 3 1.33 80.89 Cutting et al. 1990 2789+5G--~A intron 14b 3 1.33 82.22 Highsmith* Q552X 11 3 1.33 83.56 Devoto et al. 1991 621+lG---~T intron 4 2 0.89 84.44 Zielenski et al. 1991b W1282X 20 2 0.89 85.33 Vidaud et al. 1990 3132delTG 17a 2 0.89 86.22 w 2790-2A---~G intron 14b 2 0.89 87.11 w 457TAT--)G 4 1 0.44 87.56 Ravnik-Glavac et al. 1993 R347P 7 1 0.44 88.00 Dean et al. 1990 G551D 11 .1 0.44 88.44 Cutting et al. 1990 1717-8G-+A intron 10 1 0.44 88.89 Savov et al. 1994 3849+ 10KbC--)T intron 19 1 0.44 89.33 Highsmith* R709X 13 1 0.44 89.78 w 1898+3A---~G intron 12 1 0.44 90.22 Cremonesi et al. 1992 Identified 203 90.22 Unidentified 22 9.78 Variatioh Exon References 1540 A orG Met or Val at 470 10 Kerem et al. 1990 1898+152 T or A intron 12 Chillon et al. 1991 2134 C or T Arg or Cys at 668 13 Fanen et al. 1992 2694 T or G No change Thr at 854 14a Zielenski et al. 199 lb 2752-22 A or G intron 14a w 3601-65 C or A intron 18 Dork et al. 199l 4029 A or G No change Thr at 1299 21 Fanen et al. 1992 4404 C or T No change Tyr at 1424 24 ShoshanP 711 +5G--+A This mutation was found in the splice donor site flanking the 3' end of exon 5. Login to comment 43 ABCC7 p.Arg709* Fig. 1 DNA sequence analyses of detected CF mutations, R709X (A) and 3132delTG (B). Login to comment 45 ABCC7 p.Arg709* In both cases, sequences of double-stranded PCR products were obtained with reverse primers Novel mutations identified during this study R709X In a 20-year-old pancreas sufficient (PS) patient, the nucleotide at position 2257 (exon 13) was changed from C to T (Fig. 1A), resulting in the replacement of Arg 709 by Stop in the R domain of the CFTR. Login to comment 51 ABCC7 p.Arg553* ABCC7 p.Arg347Glu ABCC7 p.Arg709* Genotypes were identified in six of them and were AF508/1898+3AG, R 1162X/ R347E AF508/2789 + 5G-~A, AFS08/R709X, 1717-1G--~ A/3849 + 10KbC-~T and R553X/2789 + 5G-~A. Login to comment 53 ABCC7 p.Arg347Pro In reference to the previously suggested classification of the phenotypes, whereby PS is attributable to the presence of at least one mild dominant CF allele (Kerem et al. 1989), we confirm that mutations R347P, 2789 + 5G--~A, 1898 + 3A--~G and 3849 + 10KbC--~T are all associated with a PS phenotype. Login to comment 66 ABCC7 p.Arg1162* Affected siblings were included for phenotype evaluation n Number of patients, M median, A average, FEVI forced expiratory volume in 1s (% predicted), PC Pseudomonas colonization, ABPA allergic bronchopulmonary aspergillosis, NP nasal polyposis Genotype n FEV1 PC ABPA NP AF508X&F508 25 AF508'xN1303K 8 AF508X,R1162X 7 AF508x,2183AA---~G 5 2183AA---~G'xR1162X 5 2183AA---~G",2183AA---~G 3 AF508\711 +5G---~A 3 AF508\G542X 3 Min-max M A 13-122 73.0 69.7 22 7 l 24 101 73.5 66.8 3 l 0 42- 93 74.0 69.1 3 0 1 35 107 56.0 67.0 3 1 1 3294 69.0 69.2 2 0 1 23 81 64.0 56.0 1 0 0 1588 51.5 51.5 1 0 0 29-49 43.0 40.3 1 1 0 cepacia chronic colonization, which is an important peculiarity in patients with advanced lung involvement, was present only in two AF508 homozygotes. Login to comment 83 ABCC7 p.Arg1162* However, these data could be valuable as a basis for a pilot study and they suggest the need for testing some peculiar mutations, such as R1162X and 2183AA---~G, in CF subjects of North-Eastern Italian descent. Login to comment 94 ABCC7 p.Arg709* One additional mild mutation, R709X, is reported for the first time in this paper. Login to comment 95 ABCC7 p.Arg709* We were surprised to find that a nonsense mutation such as R709X, which presumably codes for a protein truncated at the R domain, is associated with a PS phenotype. Login to comment