ABCMdb

PMID: 9521595

Onay T, Topaloglu O, Zielenski J, Gokgoz N, Kayserili H, Camcioglu Y, Cokugras H, Akcakaya N, Apak M, Tsui LC, Kirdar B
Analysis of the CFTR gene in Turkish cystic fibrosis patients: identification of three novel mutations (3172delAC, P1013L and M1028I).
Hum Genet. 1998 Feb;102(2):224-30., [PubMed]

Sentences

No. Mutations Sentence Comment

1 ABCC7 p.Pro1013Leu ABCC7 p.Met1028Ile In addition to 15 previously reported mutations and 12 polymorphisms, three novel mutations, namely 3172delAC, P1013L and M1028I, were detected. Login to comment 3 ABCC7 p.Gly542* The second most common mutation was 1677delTA, with a frequency of 7.3%, followed by G542X and 2183AA→G mutations, with frequencies of 4.9%. Login to comment 17 ABCC7 p.Pro1013Leu ABCC7 p.Met1028Ile Preliminary studies have reT. Onay · O. Topaloglu · J. Zielenski · N. Gokgoz · H. Kayserili · Y. Camcioglu · H. Cokugras · N. Akcakaya · M. Apak · L.-C. Tsui · B. Kirdar Analysis of the CFTR gene in Turkish cystic fibrosis patients: identification of three novel mutations (3172delAC, P1013L and M1028I) Hum Genet (1998) 102:224-230 (c) Springer-Verlag 1998 Received: 16 June 1997 / Accepted: 18 September 1997 ORIGINAL INVESTIGATION T. Onay · O. Topaloglu · N. Gokgoz Bogazici University, Department of Molecular Biology and Genetics, 80815 Bebek, Istanbul, Turkey J. Zielenski · L. Login to comment 26 ABCC7 p.Gly551Asp ABCC7 p.Arg553* ABCC7 p.Gly542* ABCC7 p.Ser549Asn ABCC7 p.Arg560Thr ABCC7 p.Ser549Ile Other frequent mutations, namely G542X, R560T, S549N or S549I and G551D or R553X, were analysed by the multiplex ARMS method combined with restriction enzyme analysis (Dean et al. 1990; Cutting et al. 1990; Ferrie et al. 1992). Login to comment 27 ABCC7 p.Trp1282* ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Val520Phe ABCC7 p.Cys524* For the identification of N1303K, W1282X, V520F, C524X and R334W, mutation detection methods based on the analysis of PCR products by appropriate restriction enzymes were used as previously described (Osborne et al. 1992; Shoshani et al. 1992; Picci et al. 1992; Jones et al. 1992). Login to comment 41 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Three other mutations, namely G542X, N1303K and W1282X, were found on 10 chromosomes and screening of exon 10 by DGGE resulted in the identification of the homozygous presence of 1525-1 G→A in one affected child with a sweat test score of 109 mEq/l. Login to comment 43 ABCC7 p.Thr1220Ile This study also revealed the heterozygous presence of an amino acid variation, T1220I, in one affected child. Login to comment 52 ABCC7 p.Phe1052Val This patient was found to be a compound heterozygote for 3172delAC/F1052V. Login to comment 53 ABCC7 p.Pro1013Leu P1013L A transition of C-to-T was detected at nucleotide position 3169 in exon 17a of the CFTR gene (Fig.2a). Login to comment 54 ABCC7 p.Pro1013Leu The transi- 225 tion caused a change of proline to leucine at position 1013 of the protein and was detected in one CF patient with a sweat test score of 65 mEq/l. Login to comment 56 ABCC7 p.Met1028Ile M1028I A nucleotide change, namely a G-to-T transversion at nucleotide 3286 in exon 17a of the CFTR gene, was detected in one patient who gave a high sweat test score and who had symptoms of malabsorption (Fig.2b). Login to comment 58 ABCC7 p.Met1028Ile This transition caused a change of methionine to isoleucine at position 1028 of the protein. Login to comment 64 ABCC7 p.Pro1013Leu a P1013L (antisense). Login to comment 65 ABCC7 p.Met1028Ile b M1028I (antisense) Other mutations Seventeen different mutations leading to CF in 41 of the 99 non-∆F508 chromosomes (34%) have been identified in this study. Login to comment 67 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Phe1052Val ABCC7 p.Asp110His ABCC7 p.Leu571Ser Mutations 1677delTA, G542X and 2183AA→G have frequencies greater or equal to approximately 5%, whereas F1052V, 2043delG, D110H, N1303K, L571S and 296+9 A→T have frequencies of 2%. Login to comment 69 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Leu571Ser Nine homozygous CF genotypes, for mutations ∆F508, 1677delTA, 2183AA→G, G542X, L571S, N1303K, W1282X, 1525-1 G→A and 2043 delG, were observed in 26.0% of cases. Login to comment 70 ABCC7 p.Leu571Ser Among these mutations, L571S was first reported by Angelicheva et al. (1997) in the paternal allele of a CF patient of Turkish origin and the present study shows that the homozygous presence of this mutation leads to a severe phenotype with pancreatic insufficiency and pulmonary involvement in the Turkish CF patient. Login to comment 75 ABCC7 p.Gly542* G542X 11 Gly→Stop at 542 G→T at 1756 6 (4.91) Kerem et al. 1990 5. Login to comment 76 ABCC7 p.Phe1052Val F1052V 17b Phe→Val at 1052 T→G at 3286 2 (1.64) Mercier et al. 1993 6. Login to comment 78 ABCC7 p.Asp110His D110H 4 Asp→His at 110 G→C at 460 2 (1.64) Dean et al. 1990 8. Login to comment 79 ABCC7 p.Asn1303Lys N1303K 21 Asn→Lys at 1303 C→G at 4041 2 (1.64) Osborne et al. 1992 9. Login to comment 80 ABCC7 p.Leu571Ser L571S 12 Leu→Ser at 571 T→C at 1844 2 (1.64) Angelicheva et al. 1997 10. Login to comment 82 ABCC7 p.Met1028Ile M1028I 17a Met→Ile at 1028 G→T at 3286 1 (0.82) This study 12. Login to comment 83 ABCC7 p.Pro1013Leu P1013L 17a Pro→Leu at 1013 C→T at 3169 1 (0.82) This study 13. Login to comment 86 ABCC7 p.Trp1282* W1282X 20 Trp→Stop at 1282 G→A at 3978 1 (0.82) Vidaud et al. 1990 16. Login to comment 87 ABCC7 p.Arg75Gln R75Q 3 Arg→Gln at 75 G→A at 356 1 (0.82) Zielenskia 17. Login to comment 89 ABCC7 p.Met952Ile M952I 15 Met→Ile at 952 G→C at 2988 1 (0.82) Girodona Total: 64/122 (52.5%) a Cytic Fibrosis Genetic Analysis Consortium (CFGAC) Web site: http.//www.genet.sickkids.on.ca/cfrr/ Table 2 List of sequence polymorphisms/variations identified in this study Name of change Location Consequence Nucleotide change (%) References 1. Login to comment 101 ABCC7 p.Thr1220Ile 4700 T8/9 'UTR - 8T or 9T at position 4700 39.7 Gradea a CFGAC Web site as in Table 1 This mutation has not been observed in other populations so far. In addition to 3791 C/T (T1220I) and 2752-15 C/G, which were tentatively classified as nucleotide variations, this study has revealed the presence of 11 previously reported polymorphisms in Turkish CF chromosomes. Login to comment 115 ABCC7 p.Gly542* This study reveals the presence of mutations G542X and 2182AA→G with the same frequency (4.9%) in the Turkish population. Login to comment 117 ABCC7 p.Gly542* The frequency of G542X is 8.1% in Spain (Cassals et al. 1993), 4% in Italy, 5% in Greece (Nunes et al. 1991) and 13.5% in the Jewish population of Israel (Lerer et al. 1991). Login to comment 119 ABCC7 p.Asn1303Lys These four most common mutations in the Turkish CF population account for approximately 36% of mutations. We have found the N1303K mutation to be present in 1.6% of Turkish CF chromosomes. Login to comment 121 ABCC7 p.Asn1303Lys Analysis of 15000 CF chromosomes gathered from laboratories throughout Europe and the United States has revealed the frequency of N1303K allele as 1.5%. Login to comment 122 ABCC7 p.Asn1303Lys However, the frequency of the N1303K allele also shows significant variation between countries and ethnic groups, being more common in Mediterranean countries than in Northern Europe (Osborne et al. 1992). Login to comment 123 ABCC7 p.Asn1303Lys A similar study of Nunes et al. (1991) supports this hypothesis, since the N1303K mutation has been found to be the fourth most common mutation with a frequency of 3.2% in an analysis of five Southern Europe populations, including Albanian, Greek, Italian, Spanish and Yugoslavian populations. Login to comment 124 ABCC7 p.Phe1052Val ABCC7 p.Asp110His ABCC7 p.Leu571Ser Other mutations, namely F1052V, 2043delG, D110H, L571S and 296+9 A→T, have been detected with frequencies of 1.6% in Turkish CF chromosomes. Login to comment 127 ABCC7 p.Pro1013Leu ABCC7 p.Met1028Ile The other two mutations, P1013L and M1028I, are missense mutations and we have only indirect evidence that they might be the cause of the disease. Login to comment 128 ABCC7 p.Pro1013Leu The P1013L mutation leads to a modification of proline to leucine. Login to comment 140 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Leu571Ser Nine homozygous CF genotypes, for mutations ∆F508, 1677delTA, 2183AA→G, G542X, L571S, N1303K, W1282X, 1525-1 G→A and 2043delG, were observed in 26.0% of cases, whereas consanguinity was noted in approximately 9.6% of patients. Login to comment