ABCMdb

PMID: 20797923

Farra C, Menassa R, Awwad J, Morel Y, Salameh P, Yazbeck N, Majdalani M, Wakim R, Yunis K, Mroueh S, Cabet F
Mutational spectrum of cystic fibrosis in the Lebanese population.
J Cyst Fibros. 2010 Dec;9(6):406-10. Epub 2010 Aug 25., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys Of the 44 alleles studied, the most common mutations were: F508del (34%), N1303K (27%), W1282X (7%), and S4X (7%). Login to comment 6 ABCC7 p.Arg117His ABCC7 p.Gly542* ABCC7 p.Ser549Asn Five mutations - not previously reported in the Lebanese population - were identified; these are: S549N, G542X, 2043delG, 4016insG, and R117H-7T. Login to comment 27 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Ser549Asn ABCC7 p.Ser549Asn Family Origin Community CM Sex CF mutations Age at diagnosis CP Sweat test 1 Bekaa Maronite No M W1282X Mount Lebanon Maronite F 4010del4 M W1282X/4010del4 1 year Pu Positive 2 North Sunnite Yes M N1303K North Sunnite F N1303K M N1303K/N1303K 7 months Pu, Gi, GR Positive 3 South Shiite Yes M F508del Shiite F F508del M F508del/F508del 2 years Pu, Gi, GR Positive 4 Mount Lebanon Greek-orthodox Yes M F508del Mount Lebanon Maronite F W1282X M F508del/W1282X 2 weeks Gi Positive 5 North Sunnite No M S549N North Sunnite F G542X M S549N/G542X 19 years Pu, Gi Positive 6 Bekaa Sunnite Yes M N1303K Bekaa Sunnite F N1303K M N1303K/N1303K 8 months Gi, GR Positive 7 Beirut Maronite No M 2789+5GNA Beirut Greek-Orthodox F F508del M F508del/2789+5GNA 6 months Pu, Gi, GR Positive 8 North Sunnite Yes M 2043delG North Sunnite F 2043delG M 2043delG/2043delG 6 weeks Gi No data 9 North Sunnite Yes M R117H-7T North Sunnite F R117H-7T M R117H-7T/R117H-7T 3 months Pu Positive 10 South Sunnite Yes M 4016insG South Sunnite F 4016insG M 4016insG/4016insG 3 months Pu Positive M 4016insG/4016insG 5 months Pu Positive 11 Mount Lebanon Maronite No M N1303K Mount Lebanon Greek-Catholic F N1303K M N1303K/N1303K 3 months Pu, Gi Positive 12 North Maronite No M S4X Mount Lebanon Maronite F N1303K M N1303K/S4X 1 month Pu, Gi, Gr Positive 13 Bekaa Greek-Catholic No M F508del No data Maronite F 4010del4 F F508del/4010del4 11 months Pu, Gi Positive 14 No data Greek-Catholic No M W1282X No data Maronite F F508del F W1282X/F508del 2 years No data Positive 15 Mount Lebanon Baptist No M F508del Mount Lebanon Maronite F N1303K F F508del/N1303K 3 years Pu, Gi, Gr Positive 16 North Sunnite Yes M F508del North Sunnite F F508del F F508del/F508del 9 months Pu, Gi, Gr Negative 17 North Sunnite Yes M N1303K Sunnite F N1303K F N1303K./N1303K 2 years Pu, Gr Positive 18 North Sunnite No M F508del North Sunnite F F508del F F508del/F508del 7 months Pu, Gi, Gr Positive 19 North Maronite No M F508del No data Maronite F F508del M F508del/F508del 7 years Pu, Gi, Gr Positive 20 Beirut Maronite No data M S4X No data Maronite F S4X M S4X/S4X 9 months Pu, Gi No data (continued on next page) diagnosis was based mainly on the clinical picture according to the consensus criteria [16] and was confirmed when possible by a positive sweat chloride test. Login to comment 39 ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser549Asn These mutations were W1282X, 4010del4, N1303K, F508del, S549N, G542X, 2043delG, R117H-7T, 2789 + 5G NA, 4016insG, and S4X. Login to comment 41 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys The most common mutations were; F508del detected in 34% of the 44 alleles, N1303K in 27%, W1282X in 7%, and S4X in 7% of the alleles. Login to comment 42 ABCC7 p.Arg117His ABCC7 p.Gly542* ABCC7 p.Ser549Asn Five mutations that were not previously reported in the Lebanese population were identified, these are: S549N, G542X, 2043delG, 4016insG and R117H-7T. Login to comment 45 ABCC7 p.Trp1282* Ethnic distribution of CF mutations The mutations 4010del4, S4X, and W1282X were only present in Christian families, of Maronite and Greek-catholic origins. Login to comment 46 ABCC7 p.Asn1303Lys The mutations N1303K and F508del were detected in families from all ethnic origins in Lebanon (Table 1). Login to comment 50 ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys Table 1 (continued) Family Origin Community CM Sex CF mutations Age at diagnosis CP Sweat test 21 Beirut Sunnite Yes M N1303K Beirut Sunnite F N1303K F N1303K/N1303K 5 months Pu, Gr Negative 22 Beirut Sunnite Yes M F508del Beirut Sunnite F F508del M F508del/F508del 3 months Pu, Gi, Gr No data Table 2 Frequency of common Lebanese CFTR mutations compared to Arab CFTR mutations. Login to comment 51 ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser549Asn ABCC7 p.Met952Ile Common CFTR mutations in the Lebanese population Frequency of CF alleles (%) Lebanona Palestine [17] Jordan [24] Syria [29] Saudi Arabia, United Arab Emirates, Oman, Qatar, Kuwait, and Jordan [1] Saudi Arabia [3,25] Bahrain [27] F508 del 36.3 23.5 7.4 1 patient 12 15 7.7 W1282X 13.8 10.6 N1303K 20 21 1.5 3-14 4010del4 7.5 2.3 S4X 6.3 2789+5GNA 2.5 2043delG 2.5 7 30.8 4016insG 2.5 R117H-7T 2.5 G542X 1.3 1.2 4096-28G→A 1.3 E672del 1.3 M952I 1.3 S549N 1.3 a Mutations in a total of 80 identified CF alleles in the Lebanese population from this study combined with Desgeorges et al. (1997) [2]. Login to comment 53 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys By combining the results of our study on 22 Lebanese families with those of Desgeorges et al. from 20 families, and considering these two studies as one whole Lebanese population (total identified CF alleles=80), we can deduce that the three most frequent mutations in Lebanese families are F508del, N1303K, and W1282X accounting for 70.1% of CF alleles (Table 2). Login to comment 63 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.His139Leu In populations from Saudi Arabia, United Arab Emirates, Oman, Qatar, Kuwait, and Jordan the most commonly reported mutations were 1548delG, I123V, F508del, 3120+1G→A, and H139L; while F508del (7.4%-15%) and N1303K (1.5%-14%) are not common, and the mutation W1282X is absent from these populations (Table 2) [1,3,24-26]. Login to comment 66 ABCC7 p.His139Leu Interestingly, the two common Arab mutations 1548delG and H139L, which were not found in any Caucasian chromosomes and were suggested to originate from the native Arab population, were absent from our study [15,28]. Login to comment 68 ABCC7 p.Asn1303Lys ABCC7 p.Trp1282Lys In the Palestinian population, although F508del, N1303K, and W1282K were commonly reported; however, the third most common mutation in this population, 3120+1Kbdel8.6Kb, was not observed in the Lebanese population [17]. Login to comment 70 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Trp1282Lys In Israel, the most common mutations reported were also F508del, W1282K, and N1303K, with W1282X being the most common (31.3%-36.2%) [21,30]. Login to comment