Chromosomal Microarray in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital
Autism spectrum disorders (ASD) comprise a group of neurodevelopmental disorders (NDD) characterized by deficits in communication and social interaction, as well as repetitive and restrictive behaviors, etc. The genetic implications of ASD have been widely documented, and numerous genes have been as...
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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/2073-4425/14/4/820 |
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| author | Ana Karen Sandoval-Talamantes María Ángeles Mori Fernando Santos-Simarro Sixto García-Miñaur Elena Mansilla Jair Antonio Tenorio Carolina Peña Carmen Adan María Fernández-Elvira Inmaculada Rueda Pablo Lapunzina Julián Nevado |
| author_facet | Ana Karen Sandoval-Talamantes María Ángeles Mori Fernando Santos-Simarro Sixto García-Miñaur Elena Mansilla Jair Antonio Tenorio Carolina Peña Carmen Adan María Fernández-Elvira Inmaculada Rueda Pablo Lapunzina Julián Nevado |
| author_sort | Ana Karen Sandoval-Talamantes |
| collection | DOAJ |
| description | Autism spectrum disorders (ASD) comprise a group of neurodevelopmental disorders (NDD) characterized by deficits in communication and social interaction, as well as repetitive and restrictive behaviors, etc. The genetic implications of ASD have been widely documented, and numerous genes have been associated with it. The use of chromosomal microarray analysis (CMA) has proven to be a rapid and effective method for detecting both small and large deletions and duplications associated with ASD. In this article, we present the implementation of CMA as a first-tier test in our clinical laboratory for patients with primary ASD over a prospective period of four years. The cohort was composed of 212 individuals over 3 years of age, who met DSM-5 diagnostic criteria for ASD. The use of a customized array-CGH (comparative genomic hybridization) design (KaryoArray<sup>®</sup>) found 99 individuals (45.20%) with copy number variants (CNVs); 34 of them carried deletions (34.34%) and 65 duplications (65.65%). A total of 28 of 212 patients had pathogenic or likely pathogenic CNVs, representing approximately 13% of the cohort. In turn, 28 out of 212 (approximately 12%) had variants of uncertain clinical significance (VUS). Our findings involve clinically significant CNVs, known to cause ASD (syndromic and non-syndromic), and other CNVs previously related to other comorbidities such as epilepsy or intellectual disability (ID). Lastly, we observed new rearrangements that will enhance the information available and the collection of genes associated with this disorder. Our data also highlight that CMA could be very useful in diagnosing patients with essential/primary autism, and demonstrate the existence of substantial genetic and clinical heterogeneity in non-syndromic ASD individuals, underscoring the continued challenge for genetic laboratories in terms of its molecular diagnosis. |
| first_indexed | 2024-03-11T05:00:30Z |
| format | Article |
| id | doaj.art-cc5e6f4ed6834a75bd6d960bf408c231 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T05:00:30Z |
| publishDate | 2023-03-01 |
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| record_format | Article |
| series | Genes |
| spelling | doaj.art-cc5e6f4ed6834a75bd6d960bf408c2312023-11-17T19:22:55ZengMDPI AGGenes2073-44252023-03-0114482010.3390/genes14040820Chromosomal Microarray in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary HospitalAna Karen Sandoval-Talamantes0María Ángeles Mori1Fernando Santos-Simarro2Sixto García-Miñaur3Elena Mansilla4Jair Antonio Tenorio5Carolina Peña6Carmen Adan7María Fernández-Elvira8Inmaculada Rueda9Pablo Lapunzina10Julián Nevado11INGEMM, Institute of Medical and Molecular Genetics, La Paz University Hospital, IdiPAZ, 28046 Madrid, SpainINGEMM, Institute of Medical and Molecular Genetics, La Paz University Hospital, IdiPAZ, 28046 Madrid, SpainINGEMM, Institute of Medical and Molecular Genetics, La Paz University Hospital, IdiPAZ, 28046 Madrid, SpainINGEMM, Institute of Medical and Molecular Genetics, La Paz University Hospital, IdiPAZ, 28046 Madrid, SpainINGEMM, Institute of Medical and Molecular Genetics, La Paz University Hospital, IdiPAZ, 28046 Madrid, SpainINGEMM, Institute of Medical and Molecular Genetics, La Paz University Hospital, IdiPAZ, 28046 Madrid, SpainINGEMM, Institute of Medical and Molecular Genetics, La Paz University Hospital, IdiPAZ, 28046 Madrid, SpainINGEMM, Institute of Medical and Molecular Genetics, La Paz University Hospital, IdiPAZ, 28046 Madrid, SpainINGEMM, Institute of Medical and Molecular Genetics, La Paz University Hospital, IdiPAZ, 28046 Madrid, SpainINGEMM, Institute of Medical and Molecular Genetics, La Paz University Hospital, IdiPAZ, 28046 Madrid, SpainINGEMM, Institute of Medical and Molecular Genetics, La Paz University Hospital, IdiPAZ, 28046 Madrid, SpainINGEMM, Institute of Medical and Molecular Genetics, La Paz University Hospital, IdiPAZ, 28046 Madrid, SpainAutism spectrum disorders (ASD) comprise a group of neurodevelopmental disorders (NDD) characterized by deficits in communication and social interaction, as well as repetitive and restrictive behaviors, etc. The genetic implications of ASD have been widely documented, and numerous genes have been associated with it. The use of chromosomal microarray analysis (CMA) has proven to be a rapid and effective method for detecting both small and large deletions and duplications associated with ASD. In this article, we present the implementation of CMA as a first-tier test in our clinical laboratory for patients with primary ASD over a prospective period of four years. The cohort was composed of 212 individuals over 3 years of age, who met DSM-5 diagnostic criteria for ASD. The use of a customized array-CGH (comparative genomic hybridization) design (KaryoArray<sup>®</sup>) found 99 individuals (45.20%) with copy number variants (CNVs); 34 of them carried deletions (34.34%) and 65 duplications (65.65%). A total of 28 of 212 patients had pathogenic or likely pathogenic CNVs, representing approximately 13% of the cohort. In turn, 28 out of 212 (approximately 12%) had variants of uncertain clinical significance (VUS). Our findings involve clinically significant CNVs, known to cause ASD (syndromic and non-syndromic), and other CNVs previously related to other comorbidities such as epilepsy or intellectual disability (ID). Lastly, we observed new rearrangements that will enhance the information available and the collection of genes associated with this disorder. Our data also highlight that CMA could be very useful in diagnosing patients with essential/primary autism, and demonstrate the existence of substantial genetic and clinical heterogeneity in non-syndromic ASD individuals, underscoring the continued challenge for genetic laboratories in terms of its molecular diagnosis.https://www.mdpi.com/2073-4425/14/4/820autistic spectrum disordercopy number variationsmicroarraytertiary hospital |
| spellingShingle | Ana Karen Sandoval-Talamantes María Ángeles Mori Fernando Santos-Simarro Sixto García-Miñaur Elena Mansilla Jair Antonio Tenorio Carolina Peña Carmen Adan María Fernández-Elvira Inmaculada Rueda Pablo Lapunzina Julián Nevado Chromosomal Microarray in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital Genes autistic spectrum disorder copy number variations microarray tertiary hospital |
| title | Chromosomal Microarray in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital |
| title_full | Chromosomal Microarray in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital |
| title_fullStr | Chromosomal Microarray in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital |
| title_full_unstemmed | Chromosomal Microarray in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital |
| title_short | Chromosomal Microarray in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital |
| title_sort | chromosomal microarray in patients with non syndromic autism spectrum disorders in the clinical routine of a tertiary hospital |
| topic | autistic spectrum disorder copy number variations microarray tertiary hospital |
| url | https://www.mdpi.com/2073-4425/14/4/820 |
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