Cystic fibrosis mutation spectrum in north macedonia: A step toward personalized therapy
, , , , and | Aug 28, 2019
About this article
Article Category: Original Article
Published Online: Aug 28, 2019
Page range: 35 - 40
DOI: https://doi.org/10.2478/bjmg-2019-0009
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© 2019 Terzic M, Jakimovska M, Fustik S, Jakovska T, Sukarova-Stefanovska E, Plaseska-Karanfilska D, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
The frequency of pathogenic CFTR mutations in different ethnic cohorts in our study (316 alleles).
| Mutations | HGVS (reference sequence: LRG 663tl) | Exon/Intron | Mutation Type | Class of Mutation | Macedonian | Albanian | Othera | All Alleles |
|---|---|---|---|---|---|---|---|---|
| CFTRdele2,3 (21 kb) | c.54-5940_273+10250del | 2,3 | deletion | 4(2.1) | 1(0.9) | – | 5(1.6) | |
| E92X | c.274G>T | 4 | nonsense | – | 1(0.3) | |||
| 457TAT>G | c.325_327delTATinsG | 4 | deletion/insertion | IIb | 2(1.0) | – | 2(0.6) | |
| R117C | C.349C>T | 4 | missense | 2(1.0) | – | 2(0.6) | ||
| G126D | C.349C>T | 4 | missense | IIP | 1(0.5) | 2(1.7) | – | 3(0.9) |
| Y161D | c.481T>G | 4 | missense | IIP | 2(1.0) | – | 2(0.6) | |
| 621+1G>T | c.490+G>T | 4 | mRNA splicing defect | 2(1.0) | 1(0.9) | 1 (25.0) | 4(1.3) | |
| CFTRdele4,5,6,7,8 | c.(273+l_274-l)_1116+l_1117-l)del | 4,5,6,7,8 | deletion | Ρ | 1(0.5) | – | 1(0.3) | |
| 711+1G>T | c.579+lG>T | 5 | mRNA splicing defect | III | – | 1(0.3) | ||
| 711+3A>G | c.579+3A>G | 5 | mRNA splicing defect | 1(0.5) | 3(2.5) | – | 4(1.3) | |
| R347P | c.l040G>C | 8 | missense | 1(0.5) | 2(1.7) | – | 3(0.9) | |
| A357V | c.l070C>t | 8 | missense | 1(0.5) | – | 1(0.3) | ||
| E379X | c.ll35G>T | 9 | nonsense | Ρ | 1(0.5) | – | 1(0.3) | |
| V456F | C.1366G>T | 10 | missense | 3(1.5) | – | 3(0.9) | ||
| S466X(TAG) | C.1397C>T) | 11 | nonsense | 2(1.0) | – | 2(0.6) | ||
| F508del | C.1521_1523del | 11 | deletion | II | 143 (73.7) | 94 (79.7) | 3(75.0) | 240(75.9) |
| CFTRdele11 | c.(1392+l_1393-l)_(1584+l_1585-l)del | 11 | deletion | Ρ | – | 1(0.3) | ||
| G542X | C.1624G>T | 12 | nonsense | 8(4.1) | 3(2.5) | – | 11(3.5) | |
| 1811+1G>C | C.1679G>C | 12 | mRNA splicing defect | V | 3(1.5) | – | 3(0.9) | |
| E585X | c.l753G>T | 13 | nonsense | 1(0.5) | – | 1(0.3) | ||
| E822X | c.2464G>T | 14 | nonsense | 1(0.5) | 2(1.7) | – | 3(0.9) | |
| 2184insA | C.2052 2053insA | 14 | insertion | 2(1.0) | – | 2(0.6) | ||
| 2789+5G>A | c.2657+5G>A | 16 | mRNA splicing defect | 2(1.7) | – | 2(0.6) | ||
| p.Gly930AlafsTer48 | c.2779_2788dupCTTGCTATGG | 17 | insertion | Ρ | 1(0.5) | – | 1(0.3) | |
| R1066C | C.3196C>T | 20 | missense | II | – | 1(0.3) | ||
| R1158X | C.3472C>T | 22 | nonsense | 2(1.0) | – | 2(0.6) | ||
| 3849G>A | c.3717G>A | 22 | mRNA splicing defect | V | 2(1.0) | – | 2(0.6) | |
| 3850-1G>A | c.3718-lG>A | 22 | mRNA splicing defect | V | 1(0.5) | – | 1(0.3) | |
| N1303K | C.3909C>G | 24 | missense | II | 5(2.6) | – | 6(1.9) | |
| G1349D | c.4046G>A | 25 | missense | III | 2(0.5) | 3(2.5) | – | 5(1.6) |
The number of various CFTR genotypes and corresponding classes found in our cohort (158 patients).
| Genotype Class | Genotypes | Patients |
|---|---|---|
| I/I | G542X/E822X | |
| GF42X/R1158X | ||
| 2184insA/CFTRdele2,3 | ||
| Ι/II | F508del/G542X | |
| F508del/CFTRdele2,3 | ||
| F508de1/621+lG>T | ||
| F508del/E822X | ||
| F508del/S466X(TAG) | ||
| F508del/A357V | ||
| F508del/E92X | ||
| F508del/CFTRdelell | ||
| F508del/R1158X | ||
| F508del/E379X | ||
| F508del/CFTRdele4–8 | ||
| F508del/p.Gly930AlafsTer48 | ||
| F508del/2184insA | ||
| G542X/Y61D | ||
| E585X/G126D | ||
| I/V | 621+1G>T/1811+1G>C | |
| G542X/3850-1G>A | ||
| F508del/F508del | 91 | |
| F508del/N1303K | ||
| F508del/457TAI>G | ||
| F508del/R1066C | ||
| II/III | F508del/G1349D | |
| F508del/G126D | ||
| F508del/711+lG>T | ||
| F508del/Y161D | ||
| II/IV | F508del/V456F | |
| F508del/R117C | ||
| F508del/R347P | ||
| ΙΙ/ν | F508del/711+3A>G | |
| F508del/3849G>A | ||
| F508del/1811+3G>A | ||
| IV/IV | R347P/R347P | |
| V/V | 2789+5G>A/2789+5G>A | |