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Clinical validity assessment of genes frequently tested on intellectual disability/autism sequencing panels

Purpose - Neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and autism spectrum disorder (ASD), exhibit genetic and phenotypic heterogeneity, making them difficult to differentiate without a molecular diagnosis. The Clinical Genome Resource Intellectual Disability/Autism Gene...

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Main Authors: Riggs, Erin Rooney (Author) , Bingaman, Taylor I. (Author) , Barry, Carrie-Ann (Author) , Behlmann, Andrea (Author) , Bluske, Krista (Author) , Bostwick, Bret (Author) , Bright, Alison (Author) , Chen, Chun-An (Author) , Clause, Amanda R. (Author) , Dharmadhikari, Avinash V. (Author) , Ganapathi, Mythily (Author) , Gonzaga-Jauregui, Claudia (Author) , Grant, Andrew R. (Author) , Hughes, Madeline Y. (Author) , Kim, Se Rin (Author) , Krause, Amanda (Author) , Liao, Jun (Author) , Lumaka, Aimé (Author) , Mah, Michelle (Author) , Maloney, Caitlin M. (Author) , Mohan, Shruthi (Author) , Osei-Owusu, Ikeoluwa A. (Author) , Reble, Emma (Author) , Rennie, Olivia (Author) , Savatt, Juliann M. (Author) , Shimelis, Hermela (Author) , Siegert, Rebecca K. (Author) , Sneddon, Tam P. (Author) , Thaxton, Courtney (Author) , Toner, Kelly A. (Author) , Tran, Kien Trung (Author) , Webb, Ryan (Author) , Wilcox, Emma H. (Author) , Yin, Jiani (Author) , Zhuo, Xinming (Author) , Znidarsic, Masa (Author) , Martin, Christa Lese (Author) , Betancur, Catalina (Author) , Vorstman, Jacob A. S. (Author) , Miller, David T. (Author) , Schaaf, Christian P. (Author)
Format: Article (Journal)
Language:English
Published: 26 May 2022
In: Genetics in medicine
Year: 2022, Volume: 24, Issue: 9, Pages: 1899-1908
ISSN:1530-0366
DOI:10.1016/j.gim.2022.05.001
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.gim.2022.05.001
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1098360022007560
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Author Notes:Erin Rooney Riggs, Taylor I. Bingaman, Carrie-Ann Barry, Andrea Behlmann, Krista Bluske, Bret Bostwick, Alison Bright, Chun-An Chen, Amanda R. Clause, Avinash V. Dharmadhikari, Mythily Ganapathi, Claudia Gonzaga-Jauregui, Andrew R. Grant, Madeline Y. Hughes, Se Rin Kim, Amanda Krause, Jun Liao, Aimé Lumaka, Michelle Mah, Caitlin M. Maloney, Shruthi Mohan, Ikeoluwa A. Osei-Owusu, Emma Reble, Olivia Rennie, Juliann M. Savatt, Hermela Shimelis, Rebecca K. Siegert, Tam P. Sneddon, Courtney Thaxton, Kelly A. Toner, Kien Trung Tran, Ryan Webb, Emma H. Wilcox, Jiani Yin, Xinming Zhuo, Masa Znidarsic, Christa Lese Martin, Catalina Betancur, Jacob A. S. Vorstman, David T. Miller, Christian P. Schaaf
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Summary:Purpose - Neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and autism spectrum disorder (ASD), exhibit genetic and phenotypic heterogeneity, making them difficult to differentiate without a molecular diagnosis. The Clinical Genome Resource Intellectual Disability/Autism Gene Curation Expert Panel (GCEP) uses systematic curation to distinguish ID/ASD genes that are appropriate for clinical testing (ie, with substantial evidence supporting their relationship to disease) from those that are not. - Methods - Using the Clinical Genome Resource gene-disease validity curation framework, the ID/Autism GCEP classified genes frequently included on clinical ID/ASD testing panels as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship. - Results - As of September 2021, 156 gene-disease pairs have been evaluated. Although most (75%) were determined to have definitive roles in NDDs, 22 (14%) genes evaluated had either Limited or Disputed evidence. Such genes are currently not recommended for use in clinical testing owing to the limited ability to assess the effect of identified variants. - Conclusion - Our understanding of gene-disease relationships evolves over time; new relationships are discovered and previously-held conclusions may be questioned. Without periodic re-examination, inaccurate gene-disease claims may be perpetuated. The ID/Autism GCEP will continue to evaluate these claims to improve diagnosis and clinical care for NDDs.
Item Description:Gesehen am 15.11.2022
Physical Description:Online Resource
ISSN:1530-0366
DOI:10.1016/j.gim.2022.05.001

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