Current Status of Genetic Diagnosis Laboratories and Frequency of Genetic Variants Associated with Cystic Fibrosis through a Newborn-Screening Program in Turkey
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Sampling
2.2. Next-Generation Sequencing (NGS)
2.3. Bioinformatics Analyses
2.4. Multiplex Ligation-Dependent Probe Amplification (MLPA) Analyses
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variants | Mutation Type | ACMG Classification | Patient Numbers |
---|---|---|---|
c.2978A > C p.D993A | Missense | LP | 7 |
c.1729T > C p.Y577H | Missense | VUS | 2 |
c.3468 + 52A > C | Intronic | VUS | 2 |
c.3170C > G p.T1057R | Missense | LP | 1 |
c.2982C > G p.F994L | Missense | VUS | 1 |
c.1680 − 756C > T | Intronic | VUS | 1 |
c.2054A > G p.Q685R | Missense | LP | 1 |
c.698T > C p.L233P | Missense | LP | 1 |
c.4321delC p.R1438fs*10 | Frameshift | LP | 1 |
c.3468 + 137T > C | Intronic | VUS | 1 |
c.7A > T p.R3W | Missense | VUS | 1 |
c.1836A > T p.K612N | Missense | LP | 1 |
c.1217G > C p.G406A | Missense | VUS | 1 |
c.53 + 28A > G | Intronic | VUS | 1 |
c.3311A > G p.E1104G | Missense | LP | 1 |
Variants | Mutation Type | Number of Alleles | ACMG Classification | CFRT2 Database |
---|---|---|---|---|
p.V470M | Missense | 399 | Benign * | N/A |
p.L997F | Missense | 66 | P | Non CF-causing |
p.P1013L | Missense | 47 | P | N/A |
p.F508del | Inframe del | 42 | P | CF-causing |
p.I148T | Missense | 31 | VUS | Non CF-causing |
p.F1052V | Missense | 25 | P | Varying clinical consequence |
p.E217G | Missense | 22 | P | N/A |
p.I807M | Missense | 22 | P | Non CF-causing |
c.2657 + 5G > A | Intronic | 19 | P | CF-causing |
c.2620 − 15C > G | Intronic | 16 | P | N/A |
c.3964 − 3C > G | Intronic | 16 | P | N/A |
p.F1052L | Missense | 13 | P | N/A |
p.K68E | Missense | 13 | P | N/A |
p.D1312G | Missense | 11 | P | N/A |
p.D993A | Missense | 9 | LP | N/A |
p.M952I | Missense | 9 | P | N/A |
p.Y515 * | Nonsense | 9 | P | N/A |
c.2909 − 71G > C | Intronic | 8 | P | N/A |
c.3718 − 2477C > T | Intronic | 8 | P | CF-causing |
p.D110H | Missense | 8 | P | CF-causing |
p.D1152H | Missense | 8 | P | Varying clinical consequence |
p.K684fs*38 | Frameshift | 8 | P | N/A |
p.M348K | Missense | 8 | P | N/A |
p.W1282 * | Nonsense | 8 | P | CF-causing |
p.D806G | Missense | 7 | P | N/A |
p.G576A | Missense | 7 | VUS | Non CF-causing |
p.L732 * | Nonsense | 7 | P | CF-causing |
p.N1303K | Missense | 7 | P | CF-causing |
p.R347P | Missense | 7 | P | CF-causing |
p.I506V | Missense | 6 | VUS | N/A |
p.L633I | Missense | 6 | P | N/A |
p.R117C | Missense | 6 | P | CF-causing |
p.T388M | Missense | 6 | P | N/A |
c.489 + 3A > G | Intronic | 5 | P | Varying clinical consequence |
p.G542 * | Nonsense | 5 | P | Varying clinical consequence |
p.R668C | Missense | 5 | P | Non CF-causing |
p.R75Q | Missense | 5 | P | Non CF-causing |
p.S1235R | Missense | 5 | P | Non CF-causing |
p.S877A | Missense | 5 | VUS | N/A |
p.T1220I | Missense | 5 | VUS | N/A |
p.D513G | Missense | 4 | P | CF-causing |
p.L1034F | Missense | 4 | P | N/A |
p.P111L | Missense | 4 | P | N/A |
p.Q493P | Missense | 4 | P | N/A |
p.R117H | Missense | 4 | P | Varying clinical consequence |
p.R297Q | Missense | 4 | P | N/A |
p.W1098C | Missense | 4 | VUS | CF-causing |
p.A120T | Missense | 3 | LP | Varying clinical consequence |
p.A399V | Missense | 3 | P | N/A |
p.D836Y | Missense | 3 | P | Non CF-causing |
p.E1228G | Missense | 3 | LP | N/A |
p.E528K | Missense | 3 | LP | N/A |
p.E831 * | Nonsense | 3 | P | CF-causing |
p.E92K | Missense | 3 | P | CF-causing |
p.I1234V | Missense | 3 | P | CF-causing |
p.I853I | Synonymous | 3 | VUS | N/A |
p.L183I | Missense | 3 | P | N/A |
p.M1101R | Missense | 3 | P | CF-causing |
p.Q353 * | Nonsense | 3 | P | N/A |
p.R334W | Missense | 3 | P | CF-causing |
p.R352Q | Missense | 3 | VUS | CF-causing |
p.S955A | Missense | 3 | VUS | N/A |
p.V1198M | Missense | 3 | LP | N/A |
c.1766 + 3A > G | Intronic | 2 | P | CF-causing |
c.2491 − 51T > C | Intronic | 2 | VUS | N/A |
c.3468 + 52A > C | Intronic | 2 | VUS | N/A |
p.C866T | Missense | 2 | LP | N/A |
p.E528E | Missense | 2 | P | N/A |
p.F834L | Missense | 2 | P | N/A |
p.G1069R | Missense | 2 | P | Varying clinical consequence |
p.I1000fs*2 | Frameshift | 2 | P | N/A |
p.I1295fs *33 | Frameshift | 2 | P | N/A |
p.I752S | Missense | 2 | VUS | N/A |
p.K64E | Missense | 2 | P | N/A |
p.L137fs*15 | Frameshift | 2 | P | N/A |
p.M952T | Missense | 2 | P | Unknown significance |
p.R709 * | Nonsense | 2 | P | CF-causing |
p.R74W | Missense | 2 | P | Varying clinical consequence |
p.S1373I | Missense | 2 | LP | N/A |
p.T1019A | Missense | 2 | VUS | N/A |
p.T1057A | Missense | 2 | P | N/A |
p.T1299T | Missense | 2 | VUS | N/A |
p.T966M | Missense | 2 | VUS | N/A |
p.V201M | Missense | 2 | P | Unknown significance |
p.V754M | Missense | 2 | P | Non CF-causing |
p.Y301C | Missense | 2 | VUS | N/A |
p.Y577H | Missense | 2 | VUS | N/A |
c.1116 + 57C > G | Intronic | 1 | VUS | N/A |
c.164 + 9A > T | Intronic | 1 | VUS | N/A |
c.1680 − 756C > T | Intronic | 1 | VUS | N/A |
c.2490+5G > T | Intronic | 1 | VUS | N/A |
c.2909 − 15T > G | Intronic | 1 | VUS | N/A |
c.2989 − 3C>T | Intronic | 1 | VUS | N/A |
c.3139 + 80delA | Intronic | 1 | VUS | N/A |
c.3368 − 4A > G | Intronic | 1 | P | N/A |
c.3468 + 137T > C | Intronic | 1 | VUS | N/A |
c.3469 − 2A > G | Intronic | 1 | P | N/A |
c.3963+15T > C | Intronic | 1 | VUS | N/A |
c.490 − 165T > C | Intronic | 1 | VUS | N/A |
c.53+28A > G | Intronic | 1 | VUS | N/A |
c.870 − 1026delC | Intronic | 1 | VUS | N/A |
p.A1009T | Missense | 1 | P | N/A |
p.A1113V | Missense | 1 | VUS | N/A |
p.A1364A | Synonymous | 1 | P | N/A |
p.A455V | Missense | 1 | P | N/A |
p.D58G | Missense | 1 | P | N/A |
p.D891G | Missense | 1 | P | N/A |
p.D924N | Missense | 1 | P | Unknown significance |
p.D985E | Missense | 1 | LP | N/A |
p.E1104G | Missense | 1 | LP | N/A |
p.E1409K | Missense | 1 | P | N/A |
p.E826K | Missense | 1 | P | N/A |
p.F508C | Missense | 1 | P | Non CF-causing |
p.F994C | Missense | 1 | P | N/A |
p.F994L | Missense | 1 | VUS | N/A |
p.G314A | Missense | 1 | LP | N/A |
p.G406A | Missense | 1 | VUS | N/A |
p.G723D | Missense | 1 | LP | N/A |
p.I125T | Missense | 1 | P | N/A |
p.I521F | Missense | 1 | P | N/A |
p.K1060T | Missense | 1 | P | N/A |
p.K536E | Missense | 1 | LP | N/A |
p.K612N | Missense | 1 | LP | N/A |
p.K68N | Missense | 1 | VUS | N/A |
p.L1156F | Missense | 1 | VUS | N/A |
p.L227R | Missense | 1 | P | CF-causing |
p.L233P | Missense | 1 | LP | N/A |
p.L467F | Missense | 1 | P | N/A |
p.L568F | Missense | 1 | VUS | N/A |
p.L610I | Missense | 1 | P | N/A |
p.L88 * | Nonsense | 1 | P | CF-causing |
p.M1407T | Missense | 1 | P | N/A |
p.N1432K | Missense | 1 | P | N/A |
p.N306S | Missense | 1 | VUS | N/A |
p.N417K | Missense | 1 | VUS | N/A |
p.P111P | Synonymous | 1 | VUS | N/A |
p.P5L | Missense | 1 | P | Varying clinical consequence |
p.Q685R | Missense | 1 | LP | N/A |
p.R1162L | Missense | 1 | P | Non CF-causing |
p.R1438fs*10 | Frameshift | 1 | LP | N/A |
p.R31C | Missense | 1 | P | Non CF-causing |
p.R334Q | Missense | 1 | P | Varying clinical consequence |
p.R347H | Missense | 1 | P | CF-causing |
p.R3W | Missense | 1 | VUS | N/A |
p.R668L | Missense | 1 | P | N/A |
p.R785 * | Nonsense | 1 | P | CF-causing |
p.R997F | Missense | 1 | P | N/A |
p.S1426P | Missense | 1 | P | N/A |
p.S307N | Missense | 1 | P | N/A |
p.S912L | Missense | 1 | P | Unknown significance |
p.S945L | Missense | 1 | P | CF-causing |
p.T1057R | Missense | 1 | LP | N/A |
p.T351S | Missense | 1 | P | N/A |
p.T465N | Missense | 1 | P | N/A |
p.T760M | Missense | 1 | P | N/A |
p.V855I | Missense | 1 | VUS | N/A |
p.V920L | Missense | 1 | P | N/A |
p.V938G | Missense | 1 | LP | N/A |
p.W1098L | Missense | 1 | P | N/A |
p.Y424Y | Synonymous | 1 | P | N/A |
p.Y919C | Missense | 1 | P | N/A |
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Bozdogan, S.T.; Mujde, C.; Boga, I.; Sonmezler, O.; Hanta, A.; Rencuzogullari, C.; Ozcan, D.; Altintas, D.U.; Bisgin, A. Current Status of Genetic Diagnosis Laboratories and Frequency of Genetic Variants Associated with Cystic Fibrosis through a Newborn-Screening Program in Turkey. Genes 2021, 12, 206. https://doi.org/10.3390/genes12020206
Bozdogan ST, Mujde C, Boga I, Sonmezler O, Hanta A, Rencuzogullari C, Ozcan D, Altintas DU, Bisgin A. Current Status of Genetic Diagnosis Laboratories and Frequency of Genetic Variants Associated with Cystic Fibrosis through a Newborn-Screening Program in Turkey. Genes. 2021; 12(2):206. https://doi.org/10.3390/genes12020206
Chicago/Turabian StyleBozdogan, Sevcan Tug, Cem Mujde, Ibrahim Boga, Ozge Sonmezler, Abdullah Hanta, Cagla Rencuzogullari, Dilek Ozcan, Derya Ufuk Altintas, and Atil Bisgin. 2021. "Current Status of Genetic Diagnosis Laboratories and Frequency of Genetic Variants Associated with Cystic Fibrosis through a Newborn-Screening Program in Turkey" Genes 12, no. 2: 206. https://doi.org/10.3390/genes12020206
APA StyleBozdogan, S. T., Mujde, C., Boga, I., Sonmezler, O., Hanta, A., Rencuzogullari, C., Ozcan, D., Altintas, D. U., & Bisgin, A. (2021). Current Status of Genetic Diagnosis Laboratories and Frequency of Genetic Variants Associated with Cystic Fibrosis through a Newborn-Screening Program in Turkey. Genes, 12(2), 206. https://doi.org/10.3390/genes12020206