Expanding the Clinical and Molecular Heterogeneity of Nonsyndromic Inherited Retinal Dystrophies
| Autor: | Emilio González-García, D. Salom, Gema García-García, Teresa Jaijo, Patricia Udaondo, Roberto Gallego-Pinazo, Elena Aller, Ana Cabrera-Peset, José M. Millán, Ana Rodríguez-Muñoz |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Adolescent DNA Copy Number Variations Genetic counseling DNA Mutational Analysis Bioinformatics Pathology and Forensic Medicine Genetic Heterogeneity Young Adult 03 medical and health sciences 0302 clinical medicine PDE6B Retinal Dystrophies Retinitis pigmentosa medicine Humans Genetic Predisposition to Disease Copy-number variation Child Allele frequency Alleles Genetic Association Studies Aged business.industry Genetic Diseases Inborn High-Throughput Nucleotide Sequencing Middle Aged medicine.disease Pedigree Phenotype 030104 developmental biology Child Preschool 030220 oncology & carcinogenesis Molecular Medicine Medical genetics Female business Tomography Optical Coherence Comparative genomic hybridization |
| Zdroj: | The Journal of Molecular Diagnostics. 22:532-543 |
| ISSN: | 1525-1578 |
| DOI: | 10.1016/j.jmoldx.2020.01.003 |
| Popis: | A cohort of 172 patients diagnosed clinically with nonsyndromic retinal dystrophies, from 110 families underwent full ophthalmologic examination, including retinal imaging, electrophysiology, and optical coherence tomography, when feasible. Molecular analysis was performed using targeted next-generation sequencing (NGS). Variants were filtered and prioritized according to the minimum allele frequency, and finally classified according to the American College of Medical Genetics and Genomics guidelines. Multiplex ligation-dependent probe amplification and array comparative genomic hybridization were performed to validate copy number variations identified by NGS. The diagnostic yield of this study was 62% of studied families. Thirty novel mutations were identified. The study found phenotypic intra- and interfamilial variability in families with mutations in C1QTNF5, CERKL, and PROM1; biallelic mutations in PDE6B in a unilateral retinitis pigmentosa patient; interocular asymmetry RP in 50% of the symptomatic RPGR-mutated females; the first case with possible digenism between CNGA1 and CNGB1; and a ROM1 duplication in two unrelated retinitis pigmentosa families. Ten unrelated cases were reclassified. This study highlights the clinical utility of targeted NGS for nonsyndromic inherited retinal dystrophy cases and the importance of full ophthalmologic examination, which allows new genotype-phenotype associations and expands the knowledge of this group of disorders. Identifying the cause of disease is essential to improve patient management, provide accurate genetic counseling, and take advantage of gene therapy-based treatments. |
| Databáze: | OpenAIRE |
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