ABCMdb

PMID: 12439892

Kilinc MO, Ninis VN, Dagli E, Demirkol M, Ozkinay F, Arikan Z, Cogulu O, Huner G, Karakoc F, Tolun A
Highest heterogeneity for cystic fibrosis: 36 mutations account for 75% of all CF chromosomes in Turkish patients.
Am J Med Genet. 2002 Dec 1;113(3):250-7., 2002-12-01 [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCC7 p.Lys68Glu ABCC7 p.Gln493Pro ABCC7 p.Glu608Gly ABCC7 p.Val1147Ile Seven novel mutations were identified: four missense (K68E, Q493P, E608G, and V1147I), two splice-site (406 À3T > C and 3849 þ 5G > A), and one deletion (CFTRdele17b,18). Login to comment 8 ABCC7 p.Lys68Glu ABCC7 p.Gln493Pro ABCC7 p.Glu608Gly ABCC7 p.Val1147Ile KEY WORDS: CF; Turkish; K68E; Q493P; E608G; V1147I; 406 À 3T > C; 3849 þ 5G > A; CFTRdele17b, 18 INTRODUCTION Cystic fibrosis (CF) is the most common autosomal recessive disorder in populations with European ancestry with about 1:25 carrier frequency with regional variation. Login to comment 58 ABCC7 p.Lys68Glu Novel Mutations We identified seven novel mutations, each observed only in one CF patient of a total 260 individuals with various phenotypes such as CF, bronchiectasis and unconfirmed CF, with the exception of K68E, which we found in some patients with pulmonary disease. Login to comment 61 ABCC7 p.Lys68Glu The substituted residues in the missense mutations have been conserved in human, bovine, Xenopus, dogfish, and mouse, except for mutation K68E. Login to comment 63 ABCC7 p.Lys68Glu K68E An A ! Login to comment 68 ABCC7 p.Gln493Pro Q493P An A ! Login to comment 72 ABCC7 p.Glu608Gly ABCC7 p.Glu608Gly E608G Substitution of glycine for glutamic acid at codon 608 in exon 13 resulted from an A ! Login to comment 80 ABCC7 p.Trp1282* ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg74Trp ABCC7 p.Ile148Thr ABCC7 p.Arg1070Gln ABCC7 p.Ser1235Arg ABCC7 p.Arg1066Leu ABCC7 p.Phe1052Val ABCC7 p.Glu92Lys ABCC7 p.Pro1013Leu ABCC7 p.Asp110His ABCC7 p.Leu571Ser ABCC7 p.Ala46Asp ABCC7 p.Ile125Thr ABCC7 p.Ser466* Haplotypes Associated With the Mutations Identified in 83 Turkish CF Patients* Mutation Total number of alleles Number of alleles Number of patients Haplotypes Homo Hetero DF508 39 (23.5) 6 7 23 M 28 13 1 0 1 6 7 23 M 30 13 1 0 1 6 9 23 M 31 13 1 0 1 6 7 23 M 31 13 11 4 3 6 7 23 M 7 17 2 0 2 6 7 16 M 31 13 3 1 1 6 7 17 M 31 13 17 5 7 6 7 17 M 32 13 3 1 1 1677delTA 12 (7.2) 7 7 16 V 30 13 12 5 2 2183AA > G 7 (4.2) 7 7 16 M 30 13 1 0 1 7 9 16 M 31 13 4 2 0 7 7 16 M 32 13 2 1 0 G542X 6 (3.6) 6 7 23 M 32 13 6 3 0 F1052V 5 (3.0) 6 7 17 M 7 13 4 1 2 7 5 17 M 7 17 1 0 1 W1282X 5 (3.0) 7 7 17 M 7 17 4 1 2 7 7 17 M 7 18 1 0 1 E92K 4 (2.4) 7 7 16 V 46 13 3 1 1 7 7 17 V 46 13 1 0 1 1525 À 1G > A 4 (2.4) 7 7 17 M 7 17 4 2 0 2789 þ 5G > A 4 (2.4) 7 9 17 M 7 17 3 1 1 7 5 17 M 7 17 1 0 1 N1303K 4 (2.4) 7 7 23 M 31 13 2 0 2 6 7 22 M 30 13 1 0 1 6 7 23 M 30 13 1 0 1 A46D 3 (1.8) 6 9 23 M 31 13 1 0 1 6 7 23 M 31 13 2 1 0 2184insA 3 (1.8) 7 5 17 V 30 13 1 0 1 7 7 16 V 30 13 2 0 2 R1070Q 3 (1.8) 7 7 16 M 31 13 1 0 1 7 7 17 M 31 13 2 0 2 Q493Pa 2 (1.2) 6/7 5 16 M 46 13 2 1 0 3849 þ 5G > Aa 2 (1.2) 7 7 16 M 31 13 2 1 0 CFTRdele17b,18a 2 (1.2) 6 9 16 V - - 2 1 0 K68Ea 1 (0.6) 6 9 17 M 7 13 1 0 1 R74W 1 (0.6) 6 7 16 M 32 16 1 0 1 306delTAGA 1 (0.6) 7 7 16 M 7 17 1 0 1 D110H 1 (0.6) 7 9 16 V 30 13 1 0 1 I125T 1 (0.6) 6 7 23 V 7 16 1 0 1 406 À 3T > Ca 1 (0.6) 7 7 16 V 33 17 1 0 1 I148T 1 (0.6) 6/7 7 16/17 M 7 17/23 1 0 1 621 þ 1G > T 1 (0.6) 6 7 21 V 31 13 1 0 1 R347P 1 (0.6) 7 9 17 V 30 13 1 0 1 S466X 1 (0.6) 7 7 23 M 33 13 1 0 1 L571S 1 (0.6) 7 7 16 V 29 13 1 0 1 1717 À 1G > A 1 (0.6) 7 9 17 M 7 16 1 0 1 E608Ga 1 (0.6) 7 9 16 M/V 29/31 13 1 0 1 2043delG 1 (0.6) 7 9 17 M 7 17 1 0 1 P1013L 1 (0.6) 6 5 16 M 21 18 1 0 1 R1066L 1 (0.6) 7 7 17 M 7 13 1 0 1 3129del4 1 (0.6) 7 7 16 V 29 13 1 0 1 V1147Ia 1 (0.6) 6 7 17 M 33 17 1 0 1 S1235R 1 (0.6) 6 7 17 M 39 13 1 0 1 CFTRdele2,3 1 (0.6) 7 7 16 V 33 13 1 0 1 Total 125 (75) 125 32 61 *The order of the polymorphisms is IVS6GATT, Tn, IVS8CA, M470V, IVS17BTA and IVS17BCA. Login to comment 83 ABCC7 p.Val1147Ile V1147I A G ! Login to comment 92 ABCC7 p.Lys68Glu ABCC7 p.Gln493Pro ABCC7 p.Glu608Gly ABCC7 p.Val1147Ile Sequencing results for six of the novel CF mutations: (a) 406 À 3T > C (sense); (b) V1147I (sense); (c) K68E (sense); (d) 3849 þ 5G > A (antisense); (e) Q493P (sense); (f) E608G (sense). Login to comment 94 ABCC7 p.Lys68Glu The patient is described above as a compound heterozygote for the novel mutation K68E. Login to comment 130 ABCC7 p.Gly551Asp The prominent differences were that 1677delTA was relatively common in our patients, whereas G551D, the 5th common mutation in Europeans, was not present at all. Login to comment 131 ABCC7 p.Arg347His ABCC7 p.Glu92* Our results were quite different than those of the collaborated work on CF mutations in European countries, which reported E92X and R347H to be as frequent as 1677delTA in Turkey [Estivill et al., 1997]. Login to comment 132 ABCC7 p.Lys68Asn We found those mutations not to be frequent at all, neither was K68N, which was also reported to be frequent. Login to comment 133 ABCC7 p.Lys68Glu ABCC7 p.Glu92Lys ABCC7 p.Glu92* ABCC7 p.Lys68Asn It is most likely that E92K had been misidentified as E92X and K68E as K68N, because mutations affected the same nucleotides. Login to comment 159 ABCC7 p.Gly542* All of the mutations that are also frequent in other populations, with the exception of G542X and 1525 À 1G > A, were found to be associated with more than one haplotype, indicating that these mutations have persisted for a long time in our population. Login to comment