{rfName}
To

Indexed in

License and use

Icono OpenAccess

Citations

44

Altmetrics

Grant support

The authors would like to thank Angeles Delgado Martin and the clinical staff who made this study possible. We also thank Genycell BioTech Espana for the supply of WES reagents. This work was supported by Fundacion Mutua Madrilena (FundMM 2019), the Fundacion Alicia Koplowitz (AKOPLOWITZ18_001) and AGAUR from the Autonomous Catalan Government (2017SGR1134).

Analysis of institutional authors

Isabel Alvarez-Mora, MariaAuthor

Share

November 27, 2023
Publications
>
Article
Sí

Towards a Change in the Diagnostic Algorithm of Autism Spectrum Disorders: Evidence Supporting Whole Exome Sequencing as a First-Tier Test

Publicated to:Genes. 12 (4): - 2021-04-01 12(4), DOI: 10.3390/genes12040560

Authors: Arteche-López, A; Rodríguez, MJG; Calvin, MTS; Quesada-Espinosa, JF; Rosales, JML; Milla, CP; Gómez-Manjón, I; Mayoral, IH; de la Fuente, RP; de Bustamante, AD; Darnaude, MT; Gil-Fournier, B; León, SR; Gómez, PR; Tomillo, OS; Rufián, AJ; Cano, MIA; Alonso, RV; Morales-Pérez, P; Segura-Tudela, A; Camacho, A; Nuñez, N; Simón, R; Moreno-García, M; Alvarez-Mora, MI

Affiliations

12 Octubre Univ Hosp, Genet Dept, Madrid 28041, Spain - Author
12 Octubre Univ Hosp, Inmunol Dept, Madrid 28041, Spain - Author
12 Octubre Univ Hosp, Neurol Dept, Child Neurol Unit, Madrid 28041, Spain - Author
Canc Res Network CIBERONC, Madrid 28029, Spain - Author
Fundacio Clin Recerca Biomed, Barcelona 08036, Spain - Author
Getafe Univ Hosp, Genet Dept, Madrid 28905, Spain - Author
Hosp Clin Barcelona, Biochem & Mol Genet Dept, Barcelona 08036, Spain - Author
Mostoles Univ Hosp, Genet Dept, Madrid 28935, Spain - Author
Mostoles Univ Hosp, Neuropediat Unit, Madrid 28935, Spain - Author
See more

Abstract

Autism spectrum disorder (ASD) is a prevalent and extremely heterogeneous neurodevelopmental disorder (NDD) with a strong genetic component. In recent years, the clinical relevance of de novo mutations to the aetiology of ASD has been demonstrated. Current guidelines recommend chromosomal microarray (CMA) and a FMR1 testing as first-tier tests, but there is increasing evidence that support the use of NGS for the diagnosis of NDDs. Specifically in ASD, it has not been extensively evaluated and, thus, we performed and compared the clinical utility of CMA, FMR1 testing, and/or whole exome sequencing (WES) in a cohort of 343 ASD patients. We achieved a global diagnostic rate of 12.8% (44/343), the majority of them being characterised by WES (33/44; 75%) compared to CMA (9/44; 20.4%) or FMR1 testing (2/44; 4.5%). Taking into account the age at which genetic testing was carried out, we identified a causal genetic alteration in 22.5% (37/164) of patients over 5 years old, but only in 3.9% (7/179) of patients under this age. Our data evidence the higher diagnostic power of WES compared to CMA in the study of ASD and support the implementation of WES as a first-tier test for the genetic diagnosis of this disorder, when there is no suspicion of fragile X syndrome.

Keywords

Autism spectrum disorder,diagnostic yield,exome sequencing,chromosomal microarray,fmr1 testing,copy number variationJoint consensus recommendation,chromosomal microarray,developmental-disabilities,medical genetics,american-college,de-novo,standards,association,guidelines,variant

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Genes due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position 72/175, thus managing to position itself as a Q2 (Segundo Cuartil), in the category Genetics & Heredity. Notably, the journal is positioned en el Cuartil Q2 para la agencia Scopus (SJR) en la categoría Genetics.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.13. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Field Citation Ratio (FCR) from Dimensions: 8.23 (source consulted: Dimensions Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-03, the following number of citations:

  • WoS: 15

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-08-03:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 84 (PlumX).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: Last Author (Álvarez Mora, Maria Isabel).