Effectiveness of Whole-Exome Sequencing for the Identification of Causal Mutations in Patients with Suspected Inherited Ocular Diseases
Document title: Effectiveness of Whole-Exome Sequencing for the Identification of Causal Mutations in Patients with Suspected Inherited Ocular Diseases
Journal: Revista de investigación clínica
Database: PERIÓDICA
System number: 000452951
ISSN: 0034-8376
Authors: 1
1
1
1
Institutions: 1Universidad Nacional Autónoma de México, Facultad de Medicina, Ciudad de México. México
Year:
Season: Jul-Ago
Volumen: 74
Number: 4
Pages: 219-226
Country: México
Language: Inglés
Document type: Artículo
Approach: Experimental, aplicado
English abstract Genetic eye disorders, affecting around one in 1000 people, encompass a diverse group of diseases causing severe visual deficiency. The recent adoption of next-generation sequencing techniques, including whole-exome sequencing (WES), in medicine has greatly enhanced diagnostic rates of genetically heterogeneous diseases. Objectives: The objectives of the study were to assess the diagnostic yield of WES in a cohort of Mexican individuals with suspected genetic eye disorders and to evaluate the improvement of diagnostic rates by reanalysis of WES data in patients without an initial molecular diagnosis. Methods: A total of 90 probands with ocular anomalies of suspected genetic origin were ascertained. Patients underwent WES in leukocytic DNA. Bioinformatics analysis and Sanger sequencing were used to confirm the disease-causing variants. Only variants identified as pathogenic or likely pathogenic were considered as causal. Results: Initial analysis revealed causal mutations in 46 cases (51%). Reanalysis of WES data 12 months after first analysis resulted in the identification of additional causal variants in 6 patients (7%), increasing the molecular diagnostic yield to 58%. The highest diagnostic rates by disease categories corresponded to hereditary retinal dystrophies (77%) and to anomalies of the anterior segment of the eye (47%). Conclusion: Our study demonstrates that WES is an effective approach for genetic diagnosis of genetic ocular diseases and that reanalysis of WES data can improve the diagnostic yield
Disciplines: Medicina
Keyword: Oftalmología,
Genética,
Enfermedades oculares,
Enfermedades hereditarias,
Secuenciación génica,
Exoma,
Mutaciones
Keyword: Ophthalmology,
Genetics,
Eye diseases,
Hereditary diseases,
Gene sequencing,
Exome,
Mutations
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