Diagnostic yield and variant spectrum of whole-exome sequencing in Iranian probands with congenital and…

Cohort studyMolecular genetics and metabolism reports· Sep 2026

Diagnostic yield and variant spectrum of whole-exome sequencing in Iranian probands with congenital and early-onset ocular disorders.

Ali Asadi, Seyed Ataollah Sadat Shandiz, Amirhossein Ebrahimi … Ahmad Ebrahimi

OphthalmologyCohort studyDiagnosisQ3IF 1.9

Whole-exome sequencing diagnosed 70% of unresolved inherited eye disorder cases.

Diagnostic yield and variant spectrum of whole-exome sequencing in Iranian probands with congenital and early-onset ocular disorders.

Ali Asadi … Ahmad Ebrahimi

Molecular genetics and metabolism reports · Sep 2026

Background

Inherited ocular disorders are a leading cause of early-onset visual impairment, particularly in populations with high consanguinity such as Iran, where a substantial proportion of affected individuals remain without a molecular diagnosis after conventional evaluation.

Purpose

We aimed to determine the diagnostic yield and variant spectrum of whole-exome sequencing (whole-exome sequencing) in Iranian probands with congenital or early-onset ocular disorders that were genetically unresolved by prior testing.

Methods

Thirty unrelated probands were recruited consecutively (July-September 2024).

n = 30 unrelated probands

Results

gene testing found the exact cause in about 7 of 10 patients

diagnostic yield 70 (95% CI 50.60 to 85.30)

null 0

50.60

85.30

CI excludes the null - significant

More results

Pathogenic or likely-pathogenic variants were found in established genes including ABCA4, USH2A, RP1, CRB1, CEP290, GUCY2D, CYP1B1 and TYR .

More results

Among the identified genotypes, 54% were homozygous and 12% hemizygous (X-linked), consistent with consanguinity in 11/30 (36.7%) families; 35% were single heterozygous findings in autosomal-recessive genes, interpreted as incomplete genotypes pending detection of a second allele.

Onset was infantile in 73% of probands.

“

Conclusion · 1 of 2

Whole-exome sequencing is an effective first-tier test for congenital and early-onset ocular disorders in the Iranian population, resolving roughly 70% of previously undiagnosed probands.

Conclusion · 2 of 2

Single-allele findings in recessive genes indicate that complementary copy-number and structural-variant analysis, deep-intronic assessment, periodic reanalysis, and reflex whole-genome sequencing are needed to maximise yield and support accurate genetic counselling.

Diagnostic yield and variant spectrum of whole-exome sequencing in Iranian probands with congenital and early-onset ocular disorders.

Diagnostic yield and variant spectrum of whole-exome sequencing in Iranian probands with congenital and early-onset ocular disorders.

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