Clinical and Genetic Characterisation of Cystic Fibrosis Patients in Latvia: A Twenty-Five-Year Experience
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. CF Screening Results
3.2. CFTR Genotype
3.2.1. Case 1 with Genotype c.[1521_1523delCTT];[169T>C] p.[(Phe508del)];[(Trp57Arg)], Legacy Nomenclature dF508/W57R
3.2.2. Case 2 with Genotype c.[3844T>C];[2012delT] p.[(Trp1282Arg)];[(Leu671Ter)], Legacy Nomenclature W1282R/2143delT
3.2.3. Cases 3 and 4 with Genotype c.[1521_1523delCTT];[3844T>C] p.[(Phe508del)];[(Trp1282Arg)], Legacy Nomenclature dF508/W1282R
3.2.4. Cases 5 and 6 with Genotype c.[1521_1523delCTT];[(743+1_744-1)_(1584+1_1585-1)dup] p.[(Phe508del)];[(?)], Legacy Nomenclature dF508/dup6b-10
3.2.5. Case 7 with Genotype c.[503C>A];[4004T>C] p.[(Ser168Ter)];[(Leu1335Pro)], Legacy Nomenclature Ser168Ter/L1335P
3.3. Clinical and Laboratory Characteristics of CF Patients under Regular Follow-Up
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Allele According to Legacy Nomenclature | Exon/ Intron NM_000492.3 | HGVS Nomenclature | Class of CFTR Mutation | N | % of CF-Causing Alleles in Latvia |
---|---|---|---|---|---|
W57R | 3 | c.169T>C p.(Trp57Arg) | II or III a | 2 | 1.5% |
394delTT | 3 | c.262_263delTT p.(Leu88IlefsX22) | I [15] | 1 | 0.8% |
P67L | 3 | c.200C>T p.(Pro67Leu) | II-III [4] | 1 | 0.8% |
L138ins | 4 | c.413_415dupTAC p.(Leu138dup) | II b | 1 | 0.8% |
621+1G>T | 4 | c.489+1G>T p.(?) | I [15] | 1 | 0.8% |
Ser168Ter | 5 | c.503C>A p.(Ser168Ter) | I c | 1 | 0.8% |
R334W | 8 | c.1001G>A p.(Arg334Gln) | III [15], II-III [4] | 1 | 0.8% |
A455E | 10 | c.1364C>A p.(Ala455Glu) | II [15], II-III [4] | 1 | 0.8% |
F508del | 11 | c.1521_1523delCTT p.(Phe508del) | II-III [15], II-III-VI [4] | 93 | 70.5% |
1677delTA | 11 | c.1545_1546delTA p.(Tyr515X) | I c | 2 | 1.5% |
R553X | 11 | c.1657C>T p.(Arg553X) | I c | 2 | 1.5% |
2143delT | 14 | c.2012delT p.(Leu671Ter) | I c | 2 | 1.5% |
2184insA | 14 | c.2052dupA p.(Gln685ThrfsX5) | I c | 1 | 0.8% |
R1006H | 20 | c.3197G>A p.(Arg1066His) | II-III [4] | 3 | 2.3% |
W1282X | 23 | c.3846G>A p.(Trp1282Ter) | I-II-III-VI [4] | 2 | 1.5% |
W1282R | 23 | c.3844T>C p.(Trp1282Arg) | II-III [16,17] | 2 | 1.5% |
L1335P | 25 | c.4004T>C p.(Leu1335Pro) | II d | 3 | 2.3% |
dele2,3 | covering 2nd and 3rd exons | c.54-5940_273+10250del21kb p.(Ser18ArgfsX16) | I [15] | 5 | 3.8% |
CFTRdup6b-10 | covering 7th–11th exons | c.(743+1_744-1)_(1584+1_1585-1)dup p.(?) | I c | 1 | 0.8% |
CFTRdel6b-10 | covering 7th–11th exons | c.(743+1_744-1)_(1584+1_1585-1)del p.(?) | I c | 1 | 0.8% |
3849+10kb C>T | intron between 22nd and 23rd exons | c.3718-2477C>T p.(?) | V [15] | 2 | 1.5% |
not identified | 4 | 3.0% |
Variant Legacy Name. | Variant HGVS Nomenclature | Latvia % | Estonia a % | Lithuania b % | Poland c % | Bulgaria d % | Finland e % | Russia (Ethnic) f % | Jewish g % |
---|---|---|---|---|---|---|---|---|---|
F508del | c.1521_1523delCTT p.(Phe508del) | 70.5 | 51.7 | 52 | 54.54 | 55 | 36 | 54.99 | 35.6 |
dele2,3 | c.54-5940_273+10250del21kb p.(Ser18ArgfsX16) | 3.8 | 0 | 2 | 4.47 | 0 | 5.9 | 7.59 | 0 |
R1006H | c.3197G>A p.(Arg1066His) | 2.3 | 0.017 | 0 | 0 | 0 | 0 | 0 | 0 |
L1335P | c.4004T>C p.(Leu1335Pro) | 2.3 | 0 | 0 | 0 | 0.36 | 0 | 0.22 | 0 |
W57R | c.169T>C p.(Trp57Arg) | 1.5 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
1677delTA | c.1545_1546delTA p.(Tyr515X) | 1.5 | 0 | 0 | 0 | 1.07 | 0 | 0.18 | 0 |
R553X | c.1657C>T p.(Arg553X) | 1.5 | 0 | 4.2 | 0 | 0 | 0 | 0.18 | 0 |
2143delT | c.2012delT p.(Leu671Ter) | 1.5 | 0 | 0 | 0 | 0 | 0 | 2.71 | 0 |
W1282X | c.3846G>A p.(Trp1282Ter) | 1.5 | 0 | 1 | 0.61 | 1.43 | 0 | 1.16 | 31.3 |
W1282R | c.3844T>C p.(Trp1282Arg) | 1.5 | 0 | 0 | 0 | 0 | 0 | 0.76 | 0 |
3849+10kb C>T | c.3718-2477C>T p.(?) | 1.5 | 0 | 0 | 3.93 | 1.43 | 0 | 2.35 | 4.6 |
394delTT | c.262_263delTT p.(Leu88IlefsX22) | 0.8 | 13.3 | 0 | 0 | 0 | 35 | 0.54 | 0 |
P67L | c.200C>T p.(Pro67Leu) | 0.8 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
L138ins | c.413_415dupTAC p.(Leu138dup) | 0.8 | 0 | 0 | 0 | 0 | 0 | 1.12 | 0 |
621+1G>T | c.489+1G>T p.(?) | 0.8 | 0 | 0 | 0.34 | 1.43 | 0 | 0.25 | 0 |
Ser168Ter | c.503C>A p.(Ser168Ter) | 0.8 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
R334W | c.1001G>A p.(Arg334Gln) | 0.8 | 0 | 0 | 0.41 | 0.71 | 0 | 0.69 | 0 |
A455E | c.1364C>A p.(Ala455Glu) | 0.8 | 0 | 0 | 0 | 0 | 0 | 0.04 | 0.4 |
2184insA | c.2052dupA p.(Gln685ThrfsX5) | 0.8 | 0 | 0 | 1.02 | 2.89 | 0 | 2.24 | 0 |
CFTRdup6b-10 | c.(743+1_744-1)_(1584+1_1585-1)dup p.(?) | 0.8 | 0 | 0 | 0 | 0 | 0 | 0.18 | 0 |
CFTRdel6b-10 | c.(743+1_744-1)_(1584+1_1585-1)del p.(?) | 0.8 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
not identified | 3.0 | 13.3 | 35.8 | 17.5 | 1.07 | 2.9 | 17.22 | 2.5 | |
No. of alleles analysed | 132 | 60 | 98 | 1476 | 280 | 102 | 2768 | 281 |
Characteristic | Value |
---|---|
Number of patients | 45 |
Male/female ratio | 19/26 |
Mean age at follow-up (years) ± SD (min–max) | 13.2 ± 12.2 (1.4–35) |
Mean age at diagnosis (years) (min–max) | 2.58 (0–14) |
Number of patients older than 18 years (%) | 13 (28.9%) |
Mean Z-score for BMI aged 2–17 years (min–max) | −0.4 (−2.3–1.4) |
Mean BMI aged 18 years or older ± SD (min–max) | 19.0 (15.6–23.9) |
Mean FEV1 (% predicted) ± SD (min–max) | 79.7 (18.3–111.9) |
Prevalence of Pseudomonas aeruginosa infection (%) | 10 (22.2%) |
Prevalence of Burkholderia species infection (%) | 1 (2.2%) |
Prevalence of Staphylococcus aureus infection (%) | 28 (62.2%) |
Prevalence of methicillin-resistant Staphylococcus aureus infection (%) | 1 (2.2%) |
Prevalence of non-tuberculous Mycobacterium species infection | 0 |
Prevalence of Stenotrophomonas maltophilia infection (%) | 3 (6.7%) |
Prevalence of Haemophilus influenzae infection (%) | 3 (6.7%) |
Prevalence of Achromobacter species infection (%) | 4 (8.9%) |
CF liver disease (%) | 14 (31.1%) |
CF-related diabetes mellitus (%) | 3 (6.7%) |
Pancreatic sufficient cases (%) | 3 (6.7%) |
Female patients that have given birth | 0 |
Patients born with meconium ileus (%) | 7 (15.5%) |
Patients that have undergone lung transplantation | 0 |
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Auzenbaha, M.; Aleksejeva, E.; Taurina, G.; Kornejeva, L.; Kempa, I.; Svabe, V.; Gailite, L. Clinical and Genetic Characterisation of Cystic Fibrosis Patients in Latvia: A Twenty-Five-Year Experience. Diagnostics 2022, 12, 2893. https://doi.org/10.3390/diagnostics12112893
Auzenbaha M, Aleksejeva E, Taurina G, Kornejeva L, Kempa I, Svabe V, Gailite L. Clinical and Genetic Characterisation of Cystic Fibrosis Patients in Latvia: A Twenty-Five-Year Experience. Diagnostics. 2022; 12(11):2893. https://doi.org/10.3390/diagnostics12112893
Chicago/Turabian StyleAuzenbaha, Madara, Elina Aleksejeva, Gita Taurina, Liene Kornejeva, Inga Kempa, Vija Svabe, and Linda Gailite. 2022. "Clinical and Genetic Characterisation of Cystic Fibrosis Patients in Latvia: A Twenty-Five-Year Experience" Diagnostics 12, no. 11: 2893. https://doi.org/10.3390/diagnostics12112893
APA StyleAuzenbaha, M., Aleksejeva, E., Taurina, G., Kornejeva, L., Kempa, I., Svabe, V., & Gailite, L. (2022). Clinical and Genetic Characterisation of Cystic Fibrosis Patients in Latvia: A Twenty-Five-Year Experience. Diagnostics, 12(11), 2893. https://doi.org/10.3390/diagnostics12112893