ABCMdb

PMID: 17572159

Loumi O, Ferec C, Mercier B, Creff J, Fercot B, Denine R, Grangaud JP
CFTR mutations in the Algerian population.
J Cyst Fibros. 2008 Jan;7(1):54-9. Epub 2007 Jun 14., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* CFTR mutations in the Algerian population O. Loumia,⁎, C. Ferecb,⁎, B. Mercier b , J. Creff b , B. Fercot b , R. Denine c , J.P. Grangaudd a Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumediene, Bab-Ezzouar Alger, Algérie b INSERM U613, Laboratoire de Génétique Moléculaire, 46 rue Félix Le Dantec - 29200 Brest, France c Hôpital ISSAD HASANI Beni-messous, Laboratoire de Biochimie, Algérie d Faculté de Médecine, Université d`Alger, Algérie Received 22 March 2006; received in revised form 19 April 2007; accepted 24 April 2007 Available online 14 June 2007 Abstract The nature and frequency of the major CFTR mutations in the North African population remain unclear, although a small number of CFTR mutation detection studies have been done in Algeria and Tunisia, showing largely European mutations such as F508del, G542X and N1303K, albeit at different frequencies, which presumably emerged via population admixture with Caucasians. Login to comment 16 ABCC7 p.Asn1303His ABCC7 p.Ala141Asp ABCC7 p.Thr665Ser ABCC7 p.Leu227Arg Still, 3 mutations may be specific to the Algerian [7-9] population (A141D, L227R, and N1303H) and 2 to the Tunisian population (T665S and 2766del8). Login to comment 56 ABCC7 p.Val754Met A female CF patient of Berber origin was a compound heterozygote V754M/1812-1G→A. Login to comment 58 ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Val754Met The V754M (G to A at position 2392) mutation has previously been reported to the Cystic Fibrosis Genetic Analysis Consortium by Roger Mountford and seems to confer moderate disease when it is associated either with 1812-1G→A or G542X. Login to comment 59 ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp Moreover, we have identified two complex mutations: R74W-D1270N in the mother of an Algerian F508del heterozygous CF patient, and none of these variations were inherited by the child. Login to comment 60 ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp Using intragenic polymorphisms, we have confirmed that R74W and D1270N were not inherited by the F508del heterozygous CF child. Login to comment 73 ABCC7 p.Arg117His It has previously been reported by Claustres in a CBAVD patient associated with the R117H mutation [25] and seems to confer a CF phenotype when it is associated with 2183AA/G and 621+3A/G mutations in our case. Login to comment 78 ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys In our study, we identified 9 homozygous CF patients: four F508del/F508del, one N1303K/N1303K, two 711+1G→T/ 711+1G→T, one 1609delCA/1609delCA and one W1282X/ W1282X. Login to comment 80 ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys The N1303K/N1303K homozygous patient was the 4-year-old daughter of related parents and presented pancreatic insufficiency and serious pulmonary disease with P. aeruginosa colonization. Login to comment 89 ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe Table 2 Variants detected in 36 Algerian patients (N=72 chromosomes) Variants Localisation N % T854T T→G 2694 Exon 14a 20 27.7 M470V A→G 1540 Exon 10 11 15.2 Q1463Q G→A 4521 Exon 24 9 12.5 1001+11C/T C→T 1001+11 Intron 6b 7 9.7 L997F G→C3123 exon 17a 2 2.7 875+40A/G Intron 6a 2 2.7 5T Intron 8 2 2.7 E528E G→A 1716 Exon 10 2 2.7 P1290P A→G 4002 Exon 20 1 1.3 dup1716+51→61 dup of 11 bp at 1716+51 Intron 10 0 0 N=number of chromosomes. Login to comment 90 ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Val754Met ABCC7 p.Val754Met ABCC7 p.Asp1270Asn ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp ABCC7 p.Arg74Trp ABCC7 p.Ser977Phe ABCC7 p.Ser977Phe ABCC7 p.Val562Ile ABCC7 p.Val562Ile Table 1 CFTR mutations detected in 36 Algerian patients (N=72 CF chromosomes) Mutations Substitution nucleotide Substitution amino acid Localisation N % Cum. fr. hF508del del CTT Del phe 507/508 Exon 10 12 16.7 16.7 N1303K C→G 4041 Asn→Lys 1303 Exon 21 6 8.3 25.0 711+1G→T G→T711+1 MRNA splicing defect Intron 5 6 8.3 33.3 2183AA/G del A2184 Frameshift Exon 13 3 4.2 37.5 A→G 2183 1609delCA delCA Frameshift Exon 10 2 2.8 40.3 1812-1G→A G→A 1812-1 mRNA splicing defect Intron 11 2 2.8 43.1 V562I G→A 1816 Val→Ile 562 Exon 12 2 2.8 45.9 V754M G→A 2392 Val→Met 754 Exon 13 1 1.4 47.3 W1282X G→A 3978 Trp→Stop 1282 Exon 20 3 4.2 51.5 621+3A/Ga A→G 621+3 mRNA splicing defect Intron 4 1 1.4 52.9 4332delTGa delTG4332 Frameshift Exon 23 G542X G→T 1756 Gly→Stop 542 Exon 11 1 1.4 54.3 4271delC del A 4271 Frameshift Exon 23 1 1.4 55.7 S977F C→T 3062 Ser→Phe 97 Exon 16 1 1.4 57.1 21Kb del 21-kb del Del AA E2-E3 1 1.4 58.5 R74W C→T 352 Argș2;Trp 74 Exon 3 0 0 D1270N G→A 3940 Asp→Asn 1270 Exon 20 0 0 Total 43 58.5 N=number of chromosomes; Cum. fr.=cumulative frequency. Login to comment 94 ABCC7 p.Val562Ile ABCC7 p.Val562Ile The duplication of 11 bases [1716+(51→61)] was only found in the father of a compound heterozygote V562I/S997F CF patient. Login to comment 105 ABCC7 p.Leu997Phe Only this patient has been analyzed by D-HPLC, which allowed to reveal after automatic sequencing the variant L997F. Login to comment 119 ABCC7 p.Phe508Cys Only the 5 heterozygotes have been analysed by D-HPLC and QMPSF, one of them presented a combination of sequence variation as F508C, M470V and 1525-61A/G, classified as polymorphisms in the CFGAC [27]. Login to comment 126 ABCC7 p.Asn1303Lys The N1303K mutation has already been reported to be significantly more common in Southern European populations than in Northern European populations (Cystic Fibrosis Consortium). Login to comment 130 ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe It is the third most common Table 3 CFTR mutations and variants detected in 19 patients (Na) and 26 patients (Nb) respectively with discordant and normal sweat test Na =19 % Nb =26 % Mutations ΔF508 1 2.63 1 1.92 711+1G→T 0 0 1 1.92 Variants 1001+11G/T 4 10.53 - - T854T 9 23.68 - - L997F 1 2.63 - - Table 4 CFTR mutations and variants detected in 46 Algerian obstructive azoospermia men (N=92 chromosomes) N % Cum. fr. Mutations ΔF508 2 2.17 2.17 N1303K 1 1.08 3.25 711+1G→T 2 2.17 5.43 Variants 1001+11G/T 13 14.13 T854T 18 19.56 5T 8 8.69 N=number of chromosomes; Cum. fr.=cumulative frequency. Login to comment 135 ABCC7 p.Gly551Asp ABCC7 p.Arg553* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* Surprisingly, none of the defined mutations (R553X, G551D, 1717-1G→A, G542X), which occur relatively frequently in exon 11 in Caucasian populations, was identified in our Algerian population except the G542X that has been identified once. Login to comment 140 ABCC7 p.Gly542* The 21-kb deletion seems to confer severe disease when it is associated with the G542X mutation. Login to comment 151 ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe Concerning the compound heterozygote F508del/L997F, the L997F variant has previously been reported to the CFGAC by Kabra and Castellani [35]. Login to comment 154 ABCC7 p.Leu997Phe But in our case the L997F seems to result in severe disease when associated with F508del. Login to comment