A Comprehensive, Targeted NGS Approach to Assessing Molecular Diagnosis of Lysosomal Storage Diseases
With over 60 different disorders and a combined incidence occurring in 1:5000–7000 live births, lysosomal storage diseases (LSDs) represent a major public health problem and constitute an enormous burden for affected individuals and their families. Several reasons make the diagnosis of LSDs an arduo...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/12/11/1750 |
| _version_ | 1797510238900846592 |
|---|---|
| author | Valentina La Cognata Sebastiano Cavallaro |
| author_facet | Valentina La Cognata Sebastiano Cavallaro |
| author_sort | Valentina La Cognata |
| collection | DOAJ |
| description | With over 60 different disorders and a combined incidence occurring in 1:5000–7000 live births, lysosomal storage diseases (LSDs) represent a major public health problem and constitute an enormous burden for affected individuals and their families. Several reasons make the diagnosis of LSDs an arduous task for clinicians, including the phenotype and penetrance variability, the shared signs and symptoms, and the uncertainties related to biochemical enzymatic assay results. Developing a powerful diagnostic tool based on next generation sequencing (NGS) technology may help reduce the delayed diagnostic process for these families, leading to better outcomes for current therapies and providing the basis for more appropriate genetic counseling. Herein, we employed a targeted NGS-based panel to scan the coding regions of 65 LSD-causative genes. A reference group sample (<i>n</i> = 26) with previously known genetic mutations was used to test and validate the entire workflow. Our approach demonstrated elevated analytical accuracy, sensitivity, and specificity. We believe the adoption of comprehensive targeted sequencing strategies into a routine diagnostic route may accelerate both the identification and management of LSDs with overlapping clinical profiles, producing a significant reduction in delayed diagnostic response with beneficial results in the treatment outcome. |
| first_indexed | 2024-03-10T05:28:45Z |
| format | Article |
| id | doaj.art-a48ccc852a834213ae732c5df9846587 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T05:28:45Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-a48ccc852a834213ae732c5df98465872023-11-22T23:28:17ZengMDPI AGGenes2073-44252021-10-011211175010.3390/genes12111750A Comprehensive, Targeted NGS Approach to Assessing Molecular Diagnosis of Lysosomal Storage DiseasesValentina La Cognata0Sebastiano Cavallaro1Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 95126 Catania, ItalyInstitute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 95126 Catania, ItalyWith over 60 different disorders and a combined incidence occurring in 1:5000–7000 live births, lysosomal storage diseases (LSDs) represent a major public health problem and constitute an enormous burden for affected individuals and their families. Several reasons make the diagnosis of LSDs an arduous task for clinicians, including the phenotype and penetrance variability, the shared signs and symptoms, and the uncertainties related to biochemical enzymatic assay results. Developing a powerful diagnostic tool based on next generation sequencing (NGS) technology may help reduce the delayed diagnostic process for these families, leading to better outcomes for current therapies and providing the basis for more appropriate genetic counseling. Herein, we employed a targeted NGS-based panel to scan the coding regions of 65 LSD-causative genes. A reference group sample (<i>n</i> = 26) with previously known genetic mutations was used to test and validate the entire workflow. Our approach demonstrated elevated analytical accuracy, sensitivity, and specificity. We believe the adoption of comprehensive targeted sequencing strategies into a routine diagnostic route may accelerate both the identification and management of LSDs with overlapping clinical profiles, producing a significant reduction in delayed diagnostic response with beneficial results in the treatment outcome.https://www.mdpi.com/2073-4425/12/11/1750lysosomal storage disease (LSDs)diagnosistargeted next generation sequencing (tNGS) |
| spellingShingle | Valentina La Cognata Sebastiano Cavallaro A Comprehensive, Targeted NGS Approach to Assessing Molecular Diagnosis of Lysosomal Storage Diseases Genes lysosomal storage disease (LSDs) diagnosis targeted next generation sequencing (tNGS) |
| title | A Comprehensive, Targeted NGS Approach to Assessing Molecular Diagnosis of Lysosomal Storage Diseases |
| title_full | A Comprehensive, Targeted NGS Approach to Assessing Molecular Diagnosis of Lysosomal Storage Diseases |
| title_fullStr | A Comprehensive, Targeted NGS Approach to Assessing Molecular Diagnosis of Lysosomal Storage Diseases |
| title_full_unstemmed | A Comprehensive, Targeted NGS Approach to Assessing Molecular Diagnosis of Lysosomal Storage Diseases |
| title_short | A Comprehensive, Targeted NGS Approach to Assessing Molecular Diagnosis of Lysosomal Storage Diseases |
| title_sort | comprehensive targeted ngs approach to assessing molecular diagnosis of lysosomal storage diseases |
| topic | lysosomal storage disease (LSDs) diagnosis targeted next generation sequencing (tNGS) |
| url | https://www.mdpi.com/2073-4425/12/11/1750 |
| work_keys_str_mv | AT valentinalacognata acomprehensivetargetedngsapproachtoassessingmoleculardiagnosisoflysosomalstoragediseases AT sebastianocavallaro acomprehensivetargetedngsapproachtoassessingmoleculardiagnosisoflysosomalstoragediseases AT valentinalacognata comprehensivetargetedngsapproachtoassessingmoleculardiagnosisoflysosomalstoragediseases AT sebastianocavallaro comprehensivetargetedngsapproachtoassessingmoleculardiagnosisoflysosomalstoragediseases |