Improving the Yield of Genetic Diagnosis through Additional Genetic Panel Testing in Hereditary Ophthalmic Diseases
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient and DNA Extraction
2.2. Library Preparation and Gene Panel Sequencing
2.3. Bioinformatic Analysis
2.4. Segregation Analysis
3. Results
3.1. Presumptively Genetically Diagnosed Hereditary Ophthalmic Diseases
3.2. Hereditary Ophthalmic Diseases Left with an Undiagnosed Genetic Diagnosis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene | Gene MIM | Clinical Phenotype | Phenotype MIM | Inheritance |
---|---|---|---|---|
ABCA4 | *601691 | {Macular degeneration, age-related, 2} | #153800 | AD |
Cone-rod dystrophy 3 | #604116 | AR | ||
CDH23 | *605516 | Usher syndrome, type 1D/F digenic | #601067 | AR, DR |
CLRN1 | *606397 | Retinitis pigmentosa 61 | #614180 | AR |
CRYGD | *123690 | Cataract 4, multiple types | #115700 | AD |
LSS | *600909 | Cataract 44 | #616509 | AR |
MYOC | *601652 | Glaucoma 1A, primary open angle | #137750 | AD |
OCRL | *300535 | Lowe syndrome | #309000 | XLR |
OVOL2 | *616441 | Corneal dystrophy, posterior polymorphous, 1 | #122000 | AD |
PDE6B | *180072 | Retinitis pigmentosa-40 | #613801 | AR |
Night blindness, congenital stationary, autosomal dominant 2 | #163500 | AD | ||
PRDM5 | *614161 | Brittle cornea syndrome 2 | #614170 | AR |
RP1L1 | *608581 | Occult macular dystrophy | #613587 | AD |
Retinitis pigmentosa 88 | #618826 | AR | ||
TGFBI | *601692 | Corneal dystrophy, Avellino type | #607541 | AD |
TUB | *601197 | Retinal dystrophy and obesity | #616188 | AR |
TULP1 | *602280 | Retinitis pigmentosa 14 | #600132 | AR |
Leber congenital amaurosis 15 | #613843 | AR | ||
ZNF469 | *612078 | Brittle cornea syndrome 1 | #229200 | AR |
Case | S/A | FHx | Gene | Nucleotide ID | Base Change | Codon Change | dbSNP ID | ClinVar | S | PP2 | MT | gnomAD |
---|---|---|---|---|---|---|---|---|---|---|---|---|
ad5 | F/46 | Pos | ABCA4 | NM_000350.2 | c.4297G>A | p.Val1433Ile | rs56357060 | VUS | D | P | N | 0.0017 |
fk2 | F/33 | Pos | CRYGD | NM_006891.3 | c.470G>A | p.Trp157Ter | rs121909598 | PV | na | na | na | 0.0000 |
yx9 | M/51 | Pos | MYOC | NM_000261.1 | c.1021T>C | p. Ser341Pro | rs1572210748 | LPV | D | D | D | 0.0000 |
gs6 | M/19 | Pos | OCRL | NM_000276.3 | c.2581G>A | p.Ala861Thr | rs2124430527 | PV | D | D | D | 0.0000 |
so7 | M/38 | Pos | PDE6B | NM_000283.3 | c.1488del | p.Thr497ProfsTer78 | rs730880317 | PV | na | na | na | 0.0000 |
rq2 | M/52 | Neg | RP1L1 | NM_178857.5 | c.3971A>G | p.Glu1324Gly | rs4240659 | VUS | T | B | P | 0.0000 |
nm1 | M/44 | Pos | TGFBI | NM_000358.2 | c.371G>A | p.Arg124His | rs121909211 | PV | T | D | D | 0.0000 |
Case | S/A | FHx | Gene | Nucleotide ID | Base Change | Codon Change | dbSNP ID | ClinVar | S | PP2 | MT | gnomAD |
---|---|---|---|---|---|---|---|---|---|---|---|---|
xf1 | F/49 | Neg | CDH23 | NM_022124.5 | c.9343A>G | p.Met3115Val | rs772298163 | na | D | B | D | 0.0000 |
as6 | F/51 | Neg | CLRN1 | NM_174878.2 | c.407G>A | p.Gly136Glu | rs779258184 | VUS | D | D | D | 0.0001 |
ju6 | M/34 | Neg | LSS | NM_001001438.2 | c.1120G>A | p.Asp374Asn | rs562778331 | na | D | D | D | 0.0000 |
wy5 | M/51 | Neg | OVOL2 | NM_021220.3 | c.701A>T | p.Asn234Ile | na | na | T | B | N | 0.0000 |
jh3 | M/47 | Neg | PRDM5 | NM_018699.3 | c.26G>A | p.Arg9Lys | rs1037882347 | na | D | B | D | 0.0000 |
li1 | M/44 | Neg | TUB | NM_003320.4 | c.1255C>T | p.Arg419Cys | rs1345174025 | VUS | D | D | D | 0.0000 |
pn3 | M/36 | Neg | TULP1 | NM_003322.5 | c.349G>A | p.Glu117Lys | rs527236117 | LPV | T | B | D | 0.0000 |
mk4 | F/56 | Pos | ZNF469 | NM_001367624.2 | c.9812C>T | p.Ala3271Val | rs547200758 | VUS | T | B | N | 0.0000 |
NM_001367624.2 | c.10811C>T | p.Pro3604Leu | rs957402222 | VUS | T | P | N | 0.0000 |
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Gwack, J.; Kim, N.; Park, J. Improving the Yield of Genetic Diagnosis through Additional Genetic Panel Testing in Hereditary Ophthalmic Diseases. Curr. Issues Mol. Biol. 2024, 46, 5010-5022. https://doi.org/10.3390/cimb46050300
Gwack J, Kim N, Park J. Improving the Yield of Genetic Diagnosis through Additional Genetic Panel Testing in Hereditary Ophthalmic Diseases. Current Issues in Molecular Biology. 2024; 46(5):5010-5022. https://doi.org/10.3390/cimb46050300
Chicago/Turabian StyleGwack, Jin, Namsu Kim, and Joonhong Park. 2024. "Improving the Yield of Genetic Diagnosis through Additional Genetic Panel Testing in Hereditary Ophthalmic Diseases" Current Issues in Molecular Biology 46, no. 5: 5010-5022. https://doi.org/10.3390/cimb46050300