Molecular Diagnostic Yield and Genotype-Phenotype Spectrum of Inherited Eye Diseases in a Tertiary Health Center in Türkiye.
- 1Department of Medical Genetics, Adiyaman University Faculty of Medicine, Adiyaman, Türkiye.
Abstract
Objectives
To describe ophthalmic phenotypes prompting genetic testing and to calculate the molecular diagnostic yield retrospectively in a real-world tertiary health center cohort.Methods
This retrospective observational study employed a phenotype-first review of archived clinical genetic testing records. Unique individuals with documented ocular manifestations were identified and deduplicated using demographic and phenotype consistency rather than laboratory patient number alone. Patients were assigned one primary molecular outcome: Phenotype-concordant pathogenic or likely pathogenic diagnosis, candidate/variant of uncertain significance/partial finding, unresolved, or secondary/non-diagnostic pathogenic or likely pathogenic finding. Variants of uncertain significance, single pathogenic alleles for recessive disorders, and unphased biallelic variants were not counted as definitive diagnoses.Results
Among 33 unique individuals, phenotype-concordant molecular diagnoses were established in 18.2% (6/33), while candidate, variant of uncertain significance, or partial findings were more frequent at 54.5% (18/33). Diagnoses involved REEP6, TYR, PTEN, BRPF1, and CACNA1F. An additional patient with albinism carried two heterozygous TYR pathogenic or likely pathogenic variants, but phase was not established; confirmation in trans would increase the yield to 21.2%. Excluding a CACNA1F case with a nonspecific archived phenotype reduced the yield to 15.2%.Conclusion
The conservative molecular diagnostic yield was 18.2%, with candidate and partial findings substantially outnumbering definitive diagnoses. This gap underscores the importance of phenotype concordance, inheritance-aware interpretation, and segregation analysis in real-world ophthalmic genetics, where unresolved cases represent a reanalysis cohort rather than a diagnostic dead end.
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BibTeX
@article{cevik2026molecular,
title = {{Molecular Diagnostic Yield and Genotype-Phenotype Spectrum of Inherited Eye Diseases in a Tertiary Health Center in Türkiye.}},
author = {Muhammer Özgür Çevik},
journal = {Beyoglu eye journal},
year = {2026},
month = oct,
doi = {10.14744/bej.2026.75391},
url = {https://europepmc.org/article/MED/42898535},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Molecular Diagnostic Yield and Genotype-Phenotype Spectrum of Inherited Eye Diseases in a Tertiary Health Center in Türkiye.
AU - Muhammer Özgür Çevik
PY - 2026
DA - 2026/10/01
JO - Beyoglu eye journal
DO - 10.14744/bej.2026.75391
UR - https://europepmc.org/article/MED/42898535
AB - Objectives To describe ophthalmic phenotypes prompting genetic testing and to calculate the molecular diagnostic yield retrospectively in a real-world tertiary health center cohort.Methods This retrospective observational study employed a phenotype-first review of archived clinical genetic testing records. Unique individuals with documented ocular manifestations were identified and deduplicated using demographic and phenotype consistency rather than laboratory patient number alone. Patients were assigned one primary molecular outcome: Phenotype-concordant pathogenic or likely pathogenic diagnosis, candidate/variant of uncertain significance/partial finding, unresolved, or secondary/non-diagnostic pathogenic or likely pathogenic finding. Variants of uncertain significance, single pathogenic alleles for recessive disorders, and unphased biallelic variants were not counted as definitive diagnoses.Results Among 33 unique individuals, phenotype-concordant molecular diagnoses were established in 18.2% (6/33), while candidate, variant of uncertain significance, or partial findings were more frequent at 54.5% (18/33). Diagnoses involved REEP6, TYR, PTEN, BRPF1, and CACNA1F. An additional patient with albinism carried two heterozygous TYR pathogenic or likely pathogenic variants, but phase was not established; confirmation in trans would increase the yield to 21.2%. Excluding a CACNA1F case with a nonspecific archived phenotype reduced the yield to 15.2%.Conclusion The conservative molecular diagnostic yield was 18.2%, with candidate and partial findings substantially outnumbering definitive diagnoses. This gap underscores the importance of phenotype concordance, inheritance-aware interpretation, and segregation analysis in real-world ophthalmic genetics, where unresolved cases represent a reanalysis cohort rather than a diagnostic dead end.
SN - 2459-1777
SN - 2587-0394
ER -