التفاصيل البيبلوغرافية
| العنوان: |
A Multi-Strategy Sequencing Workflow in Inherited Retinal Dystrophies: Routine Diagnosis, Addressing Unsolved Cases and Candidate Genes Identification |
| المؤلفون: |
Marta Martín-Sánchez, Nereida Bravo-Gil, María González-del Pozo, Cristina Méndez-Vidal, Elena Fernández-Suárez, Enrique Rodríguez-de la Rúa, Salud Borrego, Guillermo Antiñolo |
| المصدر: |
International Journal of Molecular Sciences; Volume 21; Issue 24; Pages: 9355 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2020 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
next generation sequencing, inherited retinal dystrophies, genetic diagnosis, WDFY3, CITED1 |
| جغرافية الموضوع: |
agris |
| الوصف: |
The management of unsolved inherited retinal dystrophies (IRD) cases is challenging since no standard pipelines have been established. This study aimed to define a diagnostic algorithm useful for the diagnostic routine and to address unsolved cases. Here, we applied a Next-Generation Sequencing-based workflow, including a first step of panel sequencing (PS) followed by clinical-exome sequencing (CES) and whole-exome sequencing (WES), in 46 IRD patients belonging to 42 families. Twenty-six likely causal variants in retinal genes were found by PS and CES. CES and WES allowed proposing two novel candidate loci (WDFY3 and a X-linked region including CITED1), both abundantly expressed in human retina according to RT-PCR and immunohistochemistry. After comparison studies, PS showed the best quality and cost values, CES and WES involved similar analytical efforts and WES presented the highest diagnostic yield. These results reinforce the relevance of panels as a first step in the diagnostic routine and suggest WES as the next strategy for unsolved cases, reserving CES for the simultaneous study of multiple conditions. Standardizing this algorithm would enhance the efficiency and equity of clinical genetics practice. Furthermore, the identified candidate genes could contribute to increase the diagnostic yield and expand the mutational spectrum in these disorders. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
Molecular Genetics and Genomics; https://dx.doi.org/10.3390/ijms21249355 |
| DOI: |
10.3390/ijms21249355 |
| الاتاحة: |
https://doi.org/10.3390/ijms21249355 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.2CD64CEF |
| قاعدة البيانات: |
BASE |