ABCMdb

PMID: 12215837

Scotet V, Gillet D, Dugueperoux I, Audrezet MP, Bellis G, Garnier B, Roussey M, Rault G, Parent P, De Braekeleer M, Ferec C
Spatial and temporal distribution of cystic fibrosis and of its mutations in Brittany, France: a retrospective study from 1960.
Hum Genet. 2002 Sep;111(3):247-54. Epub 2002 Aug 1., [PubMed]

Sentences

No. Mutations Sentence Comment

10 ABCC7 p.Gly551Asp ABCC7 p.Trp846* Western Brittany presented a specific spectrum of mutations: 1078delT (9.4% of mutated alleles in the diocese of Cornouaille), G551D (7.7% in the diocese of Léon), 4005+1G→A (2.9% in Cornouaille) and W846X (1.5% in western Brittany). Login to comment 99 ABCC7 p.Gly551Asp ABCC7 p.Trp846* The main mutation, viz. ∆F508, was present in 75% of chromosomes, whereas five other mutations were found with a frequency greater than or equal to 1%: 1078delT (3.8%); G551D (3.7%), N1303 K (1.3%), W846X (1.1%) and 2789+5G→A (1.0%). Login to comment 103 ABCC7 p.Gly551Asp Only three genotypes were responsible for two thirds of CF cases in the region: ∆F508/∆F508 (57.6%), ∆F508/1078delT (4.9%) and ∆F508/ G551D (4.7%). Login to comment 114 ABCC7 p.Gly551Asp The G551D mutation appeared to be concentrated along the coasts of North Finistère, in Léon (7.7% of mutated alleles). Login to comment 118 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly85Glu ABCC7 p.Tyr1092* ABCC7 p.Ser945Leu ABCC7 p.Ile1234Val ABCC7 p.Gly91Arg ABCC7 p.Trp846* ABCC7 p.Glu60* ABCC7 p.Arg560Lys ABCC7 p.Ser492Phe ABCC7 p.Gly1249Arg ABCC7 p.Ala72Asp ABCC7 p.Phe311Leu His genotype was ∆F508/∆F508 Mutation Exon Basse-Bretagne Haute-Bretagne Brittanya ∆F508 10 446 75.6% 224 73.7% 672 75.0% 1078delT 7 31 5.3% 3 1.0% 34 3.8% G551D 11 21 3.6% 12 3.9% 33 3.7% N1303K 21 3 0.5% 9 3.0% 12 1.3% W846X 14a 9 1.5% 1 0.3% 10 1.1% 2789+5G→A 14b 3 0.5% 6 2.0% 9 1.0% 1717-1G→A 11 5 0.8% 3 1.0% 8 0.9% Y1092X 17b 1 0.2% 6 2.0% 7 0.8% 4005+1G→A 20 6 1.0% 1 0.3% 7 0.8% E60X 3 3 0.5% 3 1.0% 6 0.7% 621+1G→T 4 3 0.5% 3 1.0% 6 0.7% R347H 7 6 1.0% 0 0.0% 6 0.7% S492F 10 2 0.3% 3 1.0% 5 0.6% G542X 11 4 0.7% 1 0.3% 5 0.6% 3272-26A→G 17b 2 0.3% 3 1.0% 5 0.6% R117H 4 3 0.5% 1 0.3% 4 0.4% G91R 3 3 0.5% 0 0.0% 3 0.3% ∆I507 10 1 0.2% 2 0.7% 3 0.3% R553X 11 3 0.5% 0 0.0% 3 0.3% W1282X 20 2 0.3% 1 0.3% 3 0.3% A72D 3 0 0.0% 2 0.7% 2 0.2% G85E 3 0 0.0% 2 0.7% 2 0.2% F311L 7 0 0.0% 2 0.7% 2 0.2% 1221delCT 7 2 0.3% 0 0.0% 2 0.2% R560K 11 0 0.0% 2 0.7% 2 0.2% 2622+1G→A 13 2 0.3% 0 0.0% 2 0.2% S945L 15 0 0.0% 2 0.7% 2 0.2% I1234V 19 2 0.3% 0 0.0% 2 0.2% G1249R 20 2 0.3% 0 0.0% 2 0.2% 3905insT 20 2 0.3% 0 0.0% 2 0.2% Unidentified - 3 0.5% 0 0.0% 3 0.3% Total - 590 65.7% 304 34.3% 896 100% IVS17bTA, IVS17bCA) of Irish, Scottish, English, Breton and Czech subjects who were carriers of this mutation, and showed that all these alleles carried a unique haplotype (16-7-17), testifying to the Celtic origin of this mutation (Cashman et al. 1995). Login to comment 119 ABCC7 p.Trp846* The W846X mutation seemed to be concentrated at the junction of the three departments of western Brittany: it was present on 1.5% of chromosomes in Basse-Bretagne but only on 0.3% in Haute-Bretagne. Login to comment 120 ABCC7 p.Tyr1092* In contrast, the eastern part of the region presented a significantly higher frequency of the N1303 K and Y1092X mutations (respectively, 3.0% vs 0.5%, P=0.0067, and 2.0% vs 0.2%, P=0.012). Login to comment 123 ABCC7 p.Gly551Asp ABCC7 p.Trp846* Consequently, western Brittany showed a specific mutation spectrum containing the mutations 1078delT (9.4% of mutated alleles in the diocese of Cornouaille), G551D (7.7% in the diocese of Léon), 4005+1G→A (2.9% in Cornouaille) and W846X (1.5% in western Brittany). Login to comment 155 ABCC7 p.Gly551Asp ABCC7 p.Trp846* Some mutations that are rare in France have a high frequency of occurrence in the Breton population (1078delT: 3.8%; G551D: 3.7%; W846X: 1.1%). Login to comment 157 ABCC7 p.Gly551Asp ABCC7 p.Trp846* Indeed, 34 of the 49 cases of the 1078delT mutation observed in France (69.4%) have been found here, together with 33 of the 73 G551D alleles (45.2%) and 10 of the 20 W846X alleles (50%; Claustres et al. 2000). Login to comment 161 ABCC7 p.Gly542* The G542X mutation, which is the most frequent in France after the ∆F508 deletion (2.9%), is solely present on 0.6% of the mutated alleles in the population studied here. Login to comment 164 ABCC7 p.Asn1303Lys The distribution and the frequency of some mutations observed in the east of Brittany are close to those observed at the national level (2789+5G→A, N1303K, ∆I507). Login to comment 167 ABCC7 p.Trp846* This high frequency could result from founder effects and genetic drifts, as illustrated by the high frequency of several mutations (e.g. 1078delT, W846X). Login to comment