ABCMdb

PMID: 15698946

des Georges M, Guittard C, Altieri JP, Templin C, Sarles J, Sarda P, Claustres M
High heterogeneity of CFTR mutations and unexpected low incidence of cystic fibrosis in the Mediterranean France.
J Cyst Fibros. 2004 Dec;3(4):265-72., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* The frequency of p.F508del was 60.23% in L-R versus 67.18% in the whole country and only five other mutations (p.G542X, p.N1303K, p.R334W, c.1717-1GNA, c.711+1GNT) had a frequency higher than 1%. Login to comment 38 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Ser1251Asn ABCC7 p.Glu60* The 20 most common mutations responsible for CF worldwide were investigated by amplification refractory mutation system (ARMS) and migration on agarose gel (Kit Elucigene CF20, including mutations c.1717-1GNA, p.G542X, p.W1282X, p.N1303K, p.F508del, c.3849+10kbCNT, c.621+1GNT, p.R553X, p.G551D, p.R117H, p.R1162X, p.R334W, p.A455E, c.2183AANG, c.3659delC, c.1078delT, p.I507del, p.R347P, p.S1251N, p.E60X). Login to comment 55 ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Five other mutations were found with a relative frequency higher than 1%: p.G542X (5.35%), p.N1303K (3.%), p.R334W (1.63%), c.1717-1GNA (1.40%) and c.711+1GNT (1.16%) (Table 1). Login to comment 56 ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* From Fig. 1, it can be seen that mutations p.G542X, p.N1303K, p.R334W and c.711+1GNT are more common in Mediterranean areas than in the whole country. Login to comment 66 ABCC7 p.Thr582Ile Four patients were diagnosed at age 30, 32, 34 and 41 years and the extreme age at diagnosis was 70 years, in a male who was diagnosed initially for bronchiectasis and was carrying a 5T allele in trans of a novel missense T582I. Login to comment 68 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Gly542* ABCC7 p.Glu585* ABCC7 p.Leu206Trp ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Tyr122* ABCC7 p.Pro67Leu ABCC7 p.Arg792* ABCC7 p.Gln220* ABCC7 p.Tyr1092* ABCC7 p.Ser945Leu ABCC7 p.Lys710* ABCC7 p.Phe508Cys ABCC7 p.Asp443Tyr ABCC7 p.Ile506Thr ABCC7 p.Asp836Tyr ABCC7 p.Asp993Tyr ABCC7 p.Gln98Arg ABCC7 p.Lys830* ABCC7 p.Leu227Arg ABCC7 p.Ile175Val ABCC7 p.Thr582Ile ABCC7 p.Tyr161Asn ABCC7 p.Ser776* of chromosomes (frequency %) p.M1V 1 1 (0.23) p.M1K 1 1 (0.23) c.300delA 3 1 (0.23) p.P67L 3 1 (0.23) c.359insT 3 1 (0.23) p.G85E 3 3 (0.70) c.394delTT 3 1 (0.23) p.Q98R 4 1 (0.23) p.R117H 4 2 (0.47) p.Y122X 4 2 (0.47) p.Y161N 4 1 (0.23) c.621+1GNT intron 4 1 (0.23) c.621+2TNG intron 4 1 (0.23) p.I175V 5 2 (0.47) c.711+1GNT intron 5 5 (1.16) p.L206W 6 3 (0.70) p.Q220X 6 1 (0.23) p.L227R 6 1 (0.23) c.1078delT 7 2 (0.47) p.R334W 7 7 (1.63) p.R347P 7 2 (0.47) c.1215delG 7 1 (0.23) c.T5 intron 8 1 (0.23) p.D443Y 9 1 (0.23) p.I506T 10 1 (0.23) p.I507del 10 4 (0.93) p.F508del 10 259 (60.23) p.F508C 10 1 (0.23) c.1677delTA 10 1 (0.23) c.1717-8GNA intron 10 1 (0.23) c.1717-1GNA intron 10 6 (1.40) p.G542X 11 23 (5.35) p.S549R 11 1 (0.23) p.G551D 11 2 (0.47) p.R553X 11 1 (0.23) c1811+1.6kbANG intron 11 4 (0.93) c.1812-1GNA intron 11 1 (0.23) p.T582I 12 1 (0.23) p.E585X 12 2 (0,47) c.1898+1GNA intron 12 1 (0.23) [c.1898+5GNA ;p.E725K] intron 12 1 (0.23) c.1898+73TNG intron 12 1 (0.23) c.2183AANG 13 4 (0.93) c.2184insA 13 1 (0.23) p.K710X 13 4 (0.93) c.2423delG 13 1 (0.23) p.S776X 13 1 (0.23) c.2493ins8 13 1 (0.23) p.R792X 13 1 (0.23) p.K830X 13 1 (0.23) p.D836Y 14a 1 (0.23) p.W846X1 14a 1 (0.23) c.2711delT 14a 1 (0.23) c.2789+5GNA intron 14b 3 (0.70) p.S945L 15 3 (0.70) p.D993Y 16 1 (0.23) c.3129del4 17a 1 (0.23) c.3195del6 17a 1 (0.23) c.3272-26ANG intron 17a 1 (0.23) [c.3395insA ;pI148T] 17b/4 1 (0,23) p.Y1092X 17b 3 (0.70) Table 1 (continued) Mutation Location exon/intron No. Login to comment 69 ABCC7 p.Trp1282* ABCC7 p.Gly1244Glu ABCC7 p.Asn1303Lys ABCC7 p.Arg1162* ABCC7 p.Arg1158* ABCC7 p.Asn1303His ABCC7 p.Ile1234Val ABCC7 p.Glu1104* ABCC7 p.Gln1313* of chromosomes (frequency %) p.E1104X 17b 2 (0.47) p.R1158X 19 3 (0.70) p.R1162X 19 2 (0.47) c.3659delC 19 1 (0.23) c.3737delA 19 2 (0.47) p.I1234V 19 1 (0.23) c.3849+10kbCNT intron 19 4 (0.93) c.3850-1GNA intron 19 1 (0.23) p.G1244E 20 1 (0.23) p.W1282X 20 2 (0.47) p.N1303H 21 1 (0.23) p.N1303K 21 13 (3.02) p.Q1313X 21 1 (0.23) c.4382delA 24 1 (023) Mutations described for the first time by our laboratory appear in bold. Login to comment 75 ABCC7 p.Arg117His ABCC7 p.Arg117His The IRT-1 concentrations were higher than the cutoff in 1299 samples (0.77%) and were followed by the genetic test which detected 11 cases with two mutations: eight were homozygous for the mutation p.F508del, two were compound heterozygotes (p.I507del+p.R334W and p.G542X+ p.R117H) and one was homozygous for the mutation p.R117H associated with the 7T allele in the intron 8 polythymidine sequence (IVS8) (Table 2). Login to comment 83 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg334Trp ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gln220* ABCC7 p.Lys710* ABCC7 p.Glu1104* ABCC7 p.Glu1104* Table 2 Genotypes identified by newborn screening in 19 affected babies IRT (ng/ml) Genotypes 118 [p.F508del]+[p.F508del]a 163 [p.F508del]+[p.F508del]a N130 [p.F508del]+[p.F508del]b N130 [p.F508del]+[p.F508del]b N130 [p.F508del]+[p.F508del]b 155 [p.F508del]+[p.F508del]a 166 [p.F508del]+[p.F508del]a 109 [p.F508del]+[p.F508del]a 110 [p.F508del]+[p.F508del]a 136 [p.F508del]+[c.3007delG]a 160 [p.F508del]+[c.2622+1GNA]a 129 [p.F508del]+[c.3850-1GNA]a 151 [p.G542X]+[c.2380del8]a 131 [c.1078delT]+[p.K710X]a N130 [p.I507del]+[p.R334W]b 75 [p.G542X]+[p.R117H ;c1342-6 T7]b MI [p.E1104X]+[p.E1104X]b 84 [p.R117H; c1342-6 T7]+[p.R117H; c1342-6 T7]a 99 [c.2183AANG]+[p.Q220X]a IRT: Immunoreactive trypsinogen (cutoff: 65 ng/ml). Login to comment 87 ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gln220* ABCC7 p.Gln220* ABCC7 p.Lys710* ABCC7 p.Lys710* M. des Georges et al. / Journal of Cystic Fibrosis 3 (2004) 265-272268 in trans of p.G542X, p.K710X in trans of c.1078delT and p.Q220X in trans of c.2183AANG (Table 2). Login to comment 89 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* The mutation was p.F508del (n=47), p.G542X (n=5), p.N1303K (n=4), p.G551D (n=2), p.R334W (n=2), c.1717- 1NA (n=1), p.I507del (n=1), p.R1162X (n=1), [p.R117H;IVS8-T7] (n=8) or [p.R117H;IVS8-T5] (n=1). Login to comment 93 ABCC7 p.Glu1104* After complete DGGE scanning followed by the sequencing of exon 17b, this neonate born from consanguineous parents of North African descent was found to be homozygous for the mutation p.E1104X. Login to comment 108 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Trp846* ABCC7 p.Trp846* M. des Georges et al. / Journal of Cystic Fibrosis 3 (2004) 265-272 269 other French regions, such as c.394delTT and p.R553X in Northern France, c.1078delT, p.G551D and p.W846X in Brittany, or c3905insT in Eastern France [4] were found at very low rates in South. Login to comment 130 ABCC7 p.Tyr1092* In southern France, 4 of these 10 additional mutations have a relative frequency above 0.5%: c.711+1GNT (1.16%), c.1811+1.6kbANG (0.93%), c.2789+5GNA (0.70%) and p.Y1092X (0.70%). Login to comment 131 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Ser1251Asn ABCC7 p.Gly85Glu ABCC7 p.Tyr122* ABCC7 p.Tyr1092* ABCC7 p.Trp846* ABCC7 p.Glu60* The panel of 30 mutations (c.1717-1GNA, p.G542X, p.W1282X, p.N1303K, p.F508del, c.3849+10kbCNT, c.621+1GNT, p.R553X, p.G551D, p.R117H, p.R1162X, p.R334W, p.A455E, c.2183AANG, c.3659delC, c.1078delT, p.I507del, p.R347P, p.S1251N, p.E60X, p.Y1092X, c.394delTT, c.1811+1.6kbANG, c.3272-26ANG, c.2789+5GNA, c.3120+1GNA, c.711+ 1GNT, p.G85E, p.Y122X, p.W846X) should account for 83.32% of the CF alleles in L-R and 84.25% in the whole country. Login to comment 158 ABCC7 p.Arg117His We found the frequency of mutation R117H (12.16%) higher in the heterozygous neonates than in the CF population in France (0.16%) or in L-R (0.47%). Login to comment 159 ABCC7 p.Arg117His R117H- 7T is associated with a broad phenotypic range, from CF with suppurative lung disease to no clinical disease. Login to comment