| Title: |
Genetic testing including targeted gene panel in a diverse clinical population of children with autism spectrum disorder: Findings and implications |
| Authors: |
Kalsner, Louisa; Twachtman‐Bassett, Jennifer; Tokarski, Kristin; Stanley, Christine; Dumont‐Mathieu, Thyde; Cotney, Justin; Chamberlain, Stormy |
| Contributors: |
University of Connecticut |
| Source: |
Molecular Genetics & Genomic Medicine ; volume 6, issue 2, page 171-185 ; ISSN 2324-9269 2324-9269 |
| Publisher Information: |
Wiley |
| Publication Year: |
2017 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Background Genetic testing of children with autism spectrum disorder ( ASD ) is now standard in the clinical setting, with American College of Medical Genetics and Genomics ( ACMGG ) guidelines recommending microarray for all children, fragile X testing for boys and additional gene sequencing, including PTEN and MECP 2, in appropriate patients. Increasingly, testing utilizing high throughput sequencing, including gene panels and whole exome sequencing, are offered as well. Methods We performed genetic testing including microarray, fragile X testing and targeted gene panel, consistently sequencing 161 genes associated with ASD risk, in a clinical population of 100 well characterized children with ASD . Frequency of rare variants identified in individual genes was compared with that reported in the Exome Aggregation Consortium (Ex AC ) database. Results We did not diagnose any conditions with complete penetrance for ASD ; however, copy number variants believed to contribute to ASD risk were identified in 12%. Eleven children were found to have likely pathogenic variants on gene panel, yet, after careful analysis, none was considered likely causative of disease. KIRREL 3 variants were identified in 6.7% of children compared to 2% in Ex AC , suggesting a potential role for KIRREL 3 variants in ASD risk. Children with KIRREL 3 variants more often had minor facial dysmorphism and intellectual disability. We also observed an increase in rare variants in TSC 2 . However, analysis of variant data from the Simons Simplex Collection indicated that rare variants in TSC 2 occur more commonly in specific racial/ethnic groups, which are more prevalent in our population than in the Ex AC database. Conclusion The yield of genetic testing including microarray, fragile X (boys) and targeted gene panel was 12%. Gene panel did not increase diagnostic yield; however, we found an increase in rare variants in KIRREL 3 . Our findings reinforce the need for racial/ethnic diversity in large‐scale genomic databases used to ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/mgg3.354 |
| Availability: |
https://doi.org/10.1002/mgg3.354; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fmgg3.354; https://onlinelibrary.wiley.com/doi/pdf/10.1002/mgg3.354 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.5D61A349 |
| Database: |
BASE |