High Performance of a Dominant/X-Linked Gene Panel in Patients with Neurodevelopmental Disorders
Neurodevelopmental disorders (NDDs) affect 2–5% of the population and approximately 50% of cases are due to genetic factors. Since <i>de novo</i> pathogenic variants account for the majority of cases, a gene panel including 460 dominant and X-linked genes was designed and applied to 398...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/3/708 |
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| author | Nino Spataro Juan Pablo Trujillo-Quintero Carmen Manso Elisabeth Gabau Nuria Capdevila Victor Martinez-Glez Antoni Berenguer-Llergo Sara Reyes Anna Brunet Neus Baena Miriam Guitart Anna Ruiz |
| author_facet | Nino Spataro Juan Pablo Trujillo-Quintero Carmen Manso Elisabeth Gabau Nuria Capdevila Victor Martinez-Glez Antoni Berenguer-Llergo Sara Reyes Anna Brunet Neus Baena Miriam Guitart Anna Ruiz |
| author_sort | Nino Spataro |
| collection | DOAJ |
| description | Neurodevelopmental disorders (NDDs) affect 2–5% of the population and approximately 50% of cases are due to genetic factors. Since <i>de novo</i> pathogenic variants account for the majority of cases, a gene panel including 460 dominant and X-linked genes was designed and applied to 398 patients affected by intellectual disability (ID)/global developmental delay (GDD) and/or autism (ASD). Pathogenic variants were identified in 83 different genes showing the high genetic heterogeneity of NDDs. A molecular diagnosis was established in 28.6% of patients after high-depth sequencing and stringent variant filtering. Compared to other available gene panel solutions for NDD molecular diagnosis, our panel has a higher diagnostic yield for both ID/GDD and ASD. As reported previously, a significantly higher diagnostic yield was observed: (<i>i</i>) in patients affected by ID/GDD compared to those affected only by ASD, and (<i>ii</i>) in females despite the higher proportion of males among our patients. No differences in diagnostic rates were found between patients affected by different levels of ID severity. Interestingly, patients harboring pathogenic variants presented different phenotypic features, suggesting that deep phenotypic profiling may help in predicting the presence of a pathogenic variant. Despite the high performance of our panel, whole exome-sequencing (WES) approaches may represent a more robust solution. For this reason, we propose the list of genes included in our customized gene panel and the variant filtering procedure presented here as a first-tier approach for the molecular diagnosis of NDDs in WES studies. |
| first_indexed | 2024-03-11T06:30:19Z |
| format | Article |
| id | doaj.art-b4d48d25439c4d14869a46d2b01c1495 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T06:30:19Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-b4d48d25439c4d14869a46d2b01c14952023-11-17T11:18:20ZengMDPI AGGenes2073-44252023-03-0114370810.3390/genes14030708High Performance of a Dominant/X-Linked Gene Panel in Patients with Neurodevelopmental DisordersNino Spataro0Juan Pablo Trujillo-Quintero1Carmen Manso2Elisabeth Gabau3Nuria Capdevila4Victor Martinez-Glez5Antoni Berenguer-Llergo6Sara Reyes7Anna Brunet8Neus Baena9Miriam Guitart10Anna Ruiz11Center for Genomic Medicine, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, 08208 Sabadell, SpainCenter for Genomic Medicine, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, 08208 Sabadell, SpainCenter for Genomic Medicine, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, 08208 Sabadell, SpainPaediatric Unit, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, 08208 Sabadell, SpainCenter for Genomic Medicine, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, 08208 Sabadell, SpainCenter for Genomic Medicine, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, 08208 Sabadell, SpainRheumatology Department, Biostatistics and Bioinformatics at Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, 08208 Sabadell, SpainGenetics Unit, Laboratory Service, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, 08208 Sabadell, SpainCenter for Genomic Medicine, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, 08208 Sabadell, SpainCenter for Genomic Medicine, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, 08208 Sabadell, SpainGenetics Unit, Laboratory Service, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, 08208 Sabadell, SpainCenter for Genomic Medicine, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, 08208 Sabadell, SpainNeurodevelopmental disorders (NDDs) affect 2–5% of the population and approximately 50% of cases are due to genetic factors. Since <i>de novo</i> pathogenic variants account for the majority of cases, a gene panel including 460 dominant and X-linked genes was designed and applied to 398 patients affected by intellectual disability (ID)/global developmental delay (GDD) and/or autism (ASD). Pathogenic variants were identified in 83 different genes showing the high genetic heterogeneity of NDDs. A molecular diagnosis was established in 28.6% of patients after high-depth sequencing and stringent variant filtering. Compared to other available gene panel solutions for NDD molecular diagnosis, our panel has a higher diagnostic yield for both ID/GDD and ASD. As reported previously, a significantly higher diagnostic yield was observed: (<i>i</i>) in patients affected by ID/GDD compared to those affected only by ASD, and (<i>ii</i>) in females despite the higher proportion of males among our patients. No differences in diagnostic rates were found between patients affected by different levels of ID severity. Interestingly, patients harboring pathogenic variants presented different phenotypic features, suggesting that deep phenotypic profiling may help in predicting the presence of a pathogenic variant. Despite the high performance of our panel, whole exome-sequencing (WES) approaches may represent a more robust solution. For this reason, we propose the list of genes included in our customized gene panel and the variant filtering procedure presented here as a first-tier approach for the molecular diagnosis of NDDs in WES studies.https://www.mdpi.com/2073-4425/14/3/708neurodevelopmental disordersintellectual disabilityautismgene panelnext generation sequencingre-analysis |
| spellingShingle | Nino Spataro Juan Pablo Trujillo-Quintero Carmen Manso Elisabeth Gabau Nuria Capdevila Victor Martinez-Glez Antoni Berenguer-Llergo Sara Reyes Anna Brunet Neus Baena Miriam Guitart Anna Ruiz High Performance of a Dominant/X-Linked Gene Panel in Patients with Neurodevelopmental Disorders Genes neurodevelopmental disorders intellectual disability autism gene panel next generation sequencing re-analysis |
| title | High Performance of a Dominant/X-Linked Gene Panel in Patients with Neurodevelopmental Disorders |
| title_full | High Performance of a Dominant/X-Linked Gene Panel in Patients with Neurodevelopmental Disorders |
| title_fullStr | High Performance of a Dominant/X-Linked Gene Panel in Patients with Neurodevelopmental Disorders |
| title_full_unstemmed | High Performance of a Dominant/X-Linked Gene Panel in Patients with Neurodevelopmental Disorders |
| title_short | High Performance of a Dominant/X-Linked Gene Panel in Patients with Neurodevelopmental Disorders |
| title_sort | high performance of a dominant x linked gene panel in patients with neurodevelopmental disorders |
| topic | neurodevelopmental disorders intellectual disability autism gene panel next generation sequencing re-analysis |
| url | https://www.mdpi.com/2073-4425/14/3/708 |
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