Molecular and Clinical Characterization of CNGA3 and CNGB3 Genes in Brazilian Patients Affected with Achromatopsia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Selection
2.2. Ophthalmic Examination
2.3. Genotyping
3. Results and Discussion
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Family | ID | Age of Onset | Sings/Symptoms Onset | Current BCVA | CS (logCS) | Gene | Nucleotide and Protein Changes | Zygosity | ACMG Classification |
---|---|---|---|---|---|---|---|---|---|
RE; LE | RE; LE | ||||||||
1 | 1.1 | 9 months | Nystagmus; photophobia | 20/100; 20/100 | N/A | CNGA3 | c.67C > T (p.Arg23*) c.1687C > T (p.Arg563Cys) | heterozygous heterozygous | pathogenic pathogenic |
2 | 2.1 | 5 months | Nystagmus; photophobia | 20/400; 20/400 | 1.35; 1.50 | CNGA3 | c.1775C > T (p.Pro592Leu) c.829C > T (p.Arg277Cys) | heterozygous heterozygous | pathogenic pathogenic |
3 | 3.1 | N/A | Photophobia, color blindness | N/A | N/A | CNGA3 | c.1717T > C (p.Tyr573His) | homozygous | pathogenic |
4 | 4.1 | 3 months | Nystagmus; photophobia | 20/125; 20/125 | 1.50; 1.45 | CNGA3 | c.572G > A (p.Cys191Tyr) c.811C > G (p.Pro271Ala) | heterozygous heterozygous | pathogenic likely pathogenic |
5 | 5.1 | 3 months | Nystagmus; photophobia | 5/400; 5/400 | N/A | CNGA3 | c.1775C > T (p.Pro592Leu) | homozygous | pathogenic |
6 | 6.1 | Since birth | Nystagmus | 20/70; 20/70 | 1.60; 1.65 | CNGA3 | c.1669G > A (p.Gly557Arg) | homozygous | likely pathogenic |
7 | 7.1 | Childhood | Low central vision | 20/50; 20/150 | N/A | CNGA3 | c.1669G > A (p.Gly557Arg) c.1981C > A (p.Arg661Ser) | heterozygous heterozygous | likely pathogenic pathogenic |
8 | 8.1 | Since birth | Nystagmus; photophobia | 20/200; 20/200 | 1.30; 1.35 | CNGA3 | c.1585G > A (p.Val529Met) c.1319G > A (p.Trp440*) | heterozygous heterozygous | pathogenic pathogenic |
9 | 9.1 | 3 months | Nystagmus; photophobia | 20/200; 20/160 | 1.30; 1.25 | CNGA3 | c.1669G > A (p.Gly557Arg) c.967G > C (p.Ala323Pro) | heterozygous heterozygous | likely pathogenic likely pathogenic |
10 | 10.1 | Childhood | Photophobia; color blindness | 20/100; 20/100 | 1.30; 1.00 | CNGA3 | c.1279C > T (p.Arg427Cys) c.1717T > C (p.Tyr573His) | heterozygous heterozygous | pathogenic pathogenic |
11 | 11.1 | 2 months | Nystagmus | N/A | N/A | CNGA3 | c.1641C > A (p.Phe547Leu) | homozygous | pathogenic |
12 | 12.1 | 4 months | Nystagmus; photophobia | 20/125; 20/125 | N/A | CNGA3 | c.1981C > A (p.Arg661Ser) c.778G > A (p.Asp260Asn) | heterozygous heterozygous | pathogenic pathogenic |
13 | 13.1 | Since birth | Nystagmus | 20/400; 20/400 | 1.15; 1.30 | CNGA3 | c.1495C > T (p.Arg499*) c.572G > A (p.Cys191Tyr) | heterozygous heterozygous | pathogenic pathogenic |
14 | 14.1 | 2 years | Nystagmus; photophobia | 20/150; 20/150 | N/A | CNGA3 | c.2T > G (p.Met1?) c.1306C > T (p.Arg436Trp) | heterozygous heterozygous | likely pathogenic pathogenic |
15 | 15.1 | Since birth | Nystagmus | 20/160; 20/250 | 1.60; 1.45 | CNGA3 | c.1279C > T (p.Arg427Cys) c.1495C > T (p.Arg499*) | heterozygous heterozygous | pathogenic pathogenic |
15 | 15.2 | Since birth | Nystagmus; photophobia | HM; 20/640 | 0.0; 0.15 | CNGA3 | c.1279C > T (p.Arg427Cys) c.1495C > T (p.Arg499*) | heterozygous heterozygous | pathogenic pathogenic |
16 | 16.1 | Since birth | Nystagmus; photophobia | N/A | N/A | CNGA3 | c.1201T > C (p.Ser401Pro) | homozygous | likely pathogenic |
17 | 17.1 | 1 year | Nystagmus | 20/80; 20/100 | 1.15; 1.35 | CNGA3 | c.1279C > T (p.Arg427Cys) c.1495C > T (p.Arg499*) | heterozygous heterozygous | pathogenic pathogenic |
18 | 18.1 | Since birth | Photophobia | 20/200; 20/200 | 1.35; 1.35 | CNGA3 | c.1585G > A (p.Val529Met) c.847C > T (p.Arg238Trp) | heterozygous heterozygous | pathogenic pathogenic |
Family | ID | Age of Onset | Sings/Symptoms Onset | Current BCVA | CS (logCS) | Gene | Nucleotide and Protein Changes | Zygosity | ACMG Classification |
---|---|---|---|---|---|---|---|---|---|
19 | 19.1 | 3 months | Nystagmus; photophobia | 10/400; 10/400 | N/A | CNGB3 | c.1148delC (p.Thr383Ilefs*13) | homozygous | pathogenic |
20 | 20.1 | Since birth | Nystagmus; photophobia | 20/200; 20/150 | 1.60; 1.45 | CNGB3 | c.1148delC (p.Thr383Ilefs*13) | homozygous | pathogenic |
21 | 21.1 | Since birth | Nystagmus; photophobia | 20/400; 20/400 | N/A | CNGB3 | c.1148delC (p.Thr383Ilefs*13) c.1285delT (p.Ser429Leufs*9) | heterozygous heterozygous | pathogenic pathogenic |
22 | 22.1 | Since birth | Photophobia | 20/200; 20/400 | 1.35; 1.35 | CNGB3 | c.1148delC (p.Thr383Ilefs*13) c.2T > C (p.Met1?) | heterozygous heterozygous | pathogenic pathogenic |
23 | 23.1 | Since birth | Photophobia | 20/400; 20/200 | 1.15; 1.20 | CNGB3 | c.1148delC (p.Thr383Ilefs*13) c.903 + 1G > A (p.?) | heterozygous heterozygous | pathogenic pathogenic |
24 | 24.1 | Since birth | Nystagmus | 20/250; 20/250 | 1.30; 1.60 | CNGB3 | c.1148delC (p.Thr383Ilefs*13) | homozygous | pathogenic |
24 | 24.2 | Since birth | Nystagmus | 20/160; 20/250 | 1.45; 1.10 | CNGB3 | c.1148delC (p.Thr383Ilefs*13) | homozygous | pathogenic |
24 | 24.3 | Since birth | Nystagmus | 20/250; 20/250 | 1.30; 1.35 | CNGB3 | c.1148delC (p.Thr383Ilefs*13) | homozygous | pathogenic |
25 | 25.1 | 2 years | Nystagmus | N/A | N/A | CNGB3 | c.1148delC (p.Thr383Ilefs*13) | homozygous | pathogenic |
25 | 25.2 | 3 months | Nystagmus | N/A | N/A | CNGB3 | c.1148delC (p.Thr383Ilefs*13) | homozygous | pathogenic |
26 | 26.1 | Since birth | Nystagmus; photophobia | 20/150; 20/150 | 1.35; 1.20 | CNGB3 | c.566G > A (p.Trp189*) | homozygous | pathogenic |
27 | 27.1 | Since birth | Nystagmus; photophobia | 20/100; 20/100 | N/A | CNGB3 | c.1148delC (p.Thr383Ilefs*13) | homozygous | pathogenic |
28 | 28.1 | Since birth | Nystagmus; photophobia | 20/160; 20/160 | 1.40; 1.30 | CNGB3 | c.1148delC (p.Thr383Ilefs*13) c.566G > A (p.Trp189*) | heterozygous heterozygous | pathogenic pathogenic |
29 | 29.1 | N/A | N/A | 20/160; 20/160 | 1.20; 1.10 | CNGB3 | c.852 + 1G > T (p.?) | homozygous | pathogenic |
30 | 30.1 | N/A | Nystagmus; photophobia | CF; 20/80 | N/A | CNGB3 | c.446_447insT (p.Lys149Asnfs*30) | homozygous | pathogenic |
31 | 31.1 | 6 months | Photophobia | 20/400; 20/320 | 0.55; 1.45 | CNGB3 | c.1432C > T (p.Arg478*) | homozygous | pathogenic |
32 | 32.1 | Since birth | Nystagmus; photophobia | 20/160; 20/160 | 1.50; 1.55 | CNGB3 | c.1148delC (p.Thr383Ilefs*13) | homozygous | pathogenic |
33 | 33.1 | 4 months | Nystagmus | 20/160; 20/200 | 1.30; 1.30 | CNGB3 | c.1810C > T (p.Arg604*) | homozygous | pathogenic |
34 | 34.1 | Since birth | Photophobia | 20/125; 20/200 | 1.40; 1.20 | CNGB3 | c.1148delC (p.Thr383Ilefs*13) c.991-3T > G (p.?) | heterozygous heterozygous | pathogenic likely pathogenic |
35 | 35.1 | 2 months | Nystagmus | N/A | N/A | CNGB3 | c.566G > A (p.Trp189*) | homozygous | pathogenic |
36 | 36.1 | Since birth | Nystagmus, photophobia | 20/125; 20/100 | N/A | CNGB3 | c.1148delC (p.Thr383Ilefs*13) c.1893T > A (p.Tyr631*) | heterozygous heterozygous | pathogenic likely pathogenic (novel) |
37 | 37.1 | N/A | Photophobia; color blindness | 20/400; 20/400 | N/A | CNGB3 | c.1148delC (p.Thr383Ilefs*13) | homozygous | pathogenic |
38 | 38.1 | 4 months | Nystagmus | 20/250; 20/200 | 1.30; 1.35 | CNGB3 | c.1148delC (p.Thr383Ilefs*13) | homozygous | pathogenic |
Causative Gene | Transcript | Nucleotide Change | Consequence | Patients Evaluated | gnomAD Allele Frequency (%) | |
---|---|---|---|---|---|---|
Allele Count | Number of Homozygotes | |||||
CNGA3 | NM_001298.3 | c.67C > T | (p.Arg23*) | 1 | 0 | 0.003540 |
CNGA3 | NM_001298.3 | c.1687C > T | (p.Arg563Cys) | 1 | 0 | 0.002122 |
CNGA3 | NM_001298.2 | c.1775C > T | (p.Pro592Leu) | 3 | 1 | 0.0003980 |
CNGA3 | NM_001298.2 | c.829C > T | (p.Arg277Cys) | 1 | 0 | 0.009548 |
CNGA3 | NM_001298.2 | c.1717T > C | (p.Tyr573His) | 3 | 1 | 0.003187 |
CNGA3 | NM_001298.2 | c.572G > A | (p.Cys191Tyr) | 2 | 0 | 0.002121 |
CNGA3 | NM_001298.2 | c.811C > G | (p.Pro271Ala) | 1 | 0 | 0.01202 |
CNGA3 | NM_001298.2 | c.1669G > A | (p.Gly557Arg) | 4 | 1 | 0.01415 |
CNGA3 | NM_001298.2 | c.1981C > A | (p.Arg661Ser) | 2 | 0 | 0.03084 |
CNGA3 | NM_001298.2 | c.1585G > A | (p.Val529Met) | 2 | 0 | 0.006726 |
CNGA3 | NM_001298.2 | c.1319G > A | (p.Trp440*) | 1 | 0 | 0.0003986 |
CNGA3 | NM_001298.2 | c.967G > C | (p.Ala323Pro) | 1 | 0 | 0.009544 |
CNGA3 | NM_001298.2 | c.1279C > T | (p.Arg427Cys) | 4 | 0 | 0.03902 |
CNGA3 | NM_001298.3 | c.1641C > A | (p.Phe547Leu) | 2 | 1 | 0.01592 |
CNGA3 | NM_001298.2 | c.778G > A | (p.Asp260Asn) | 1 | 0 | 0.003182 |
CNGA3 | NM_001298.2 | c.1495C > T | (p.Arg499*) | 4 | 0 | 0.001063 |
CNGA3 | NM_001298.2 | c.2T > G | (p.Met1?) | 1 | 0 | - |
CNGA3 | NM_001298.3 | c.1306C > T | (p.Arg436Trp) | 1 | 0 | 0.009574 |
CNGA3 | NM_001298.3 | c.1201T > C | (p.Ser401Pro) | 1 | 0 | 0.0003995 |
CNGA3 | NM_001298.2 | c.847C > T | (p.Arg238Trp) | 1 | 0 | 0.009948 |
CNGB3 | NM_019098.4 | c.1148delC | (p.Thr383Ilefs*13) | 28 | 11 | 0.1750 |
CNGB3 | NM_019098.5 | c.1285delT | (p.Ser429Leufs*9) | 1 | 0 | 0.000399 |
CNGB3 | NM_019098.5 | c.2T > C | (p.Met1?) | 1 | 0 | - |
CNGB3 | NM_019098.4 | c.903 + 1G > A | (p.?) | 1 | 0 | - |
CNGB3 | NM_019098.4 | c.566G > A | (p.Trp189*) | 5 | 2 | 0.0003977 |
CNGB3 | NM_019098.4 | c.852 + 1G > T | (p.?) | 2 | 1 | - |
CNGB3 | NM_019098.4 | c.446_447insT | (p.Lys149Asnfs*30) | 2 | 1 | 0.0003977 |
CNGB3 | NM_019098.4 | c.1432C > T | (p.Arg478*) | 2 | 1 | 0.001991 |
CNGB3 | NM_019098.5 | c.1810C > T | (p.Arg604*) | 2 | 1 | 0.0007969 |
CNGB3 | NM_019098.4 | c.991-3T > G | (p.?) | 1 | 0 | 0.001338 |
CNGB3 | NM_019098.5 | c.1893T > A | (p.Tyr631*) | 1 | 0 | - |
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Amaral, R.A.S.; Motta, F.L.; Zin, O.A.; da Palma, M.M.; Rodrigues, G.D.; Sallum, J.M.F. Molecular and Clinical Characterization of CNGA3 and CNGB3 Genes in Brazilian Patients Affected with Achromatopsia. Genes 2023, 14, 1296. https://doi.org/10.3390/genes14061296
Amaral RAS, Motta FL, Zin OA, da Palma MM, Rodrigues GD, Sallum JMF. Molecular and Clinical Characterization of CNGA3 and CNGB3 Genes in Brazilian Patients Affected with Achromatopsia. Genes. 2023; 14(6):1296. https://doi.org/10.3390/genes14061296
Chicago/Turabian StyleAmaral, Rebeca A. S., Fabiana L. Motta, Olivia A. Zin, Mariana M. da Palma, Gabriela D. Rodrigues, and Juliana M. F. Sallum. 2023. "Molecular and Clinical Characterization of CNGA3 and CNGB3 Genes in Brazilian Patients Affected with Achromatopsia" Genes 14, no. 6: 1296. https://doi.org/10.3390/genes14061296
APA StyleAmaral, R. A. S., Motta, F. L., Zin, O. A., da Palma, M. M., Rodrigues, G. D., & Sallum, J. M. F. (2023). Molecular and Clinical Characterization of CNGA3 and CNGB3 Genes in Brazilian Patients Affected with Achromatopsia. Genes, 14(6), 1296. https://doi.org/10.3390/genes14061296