[article]
| Titre : |
Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder |
| Type de document : |
texte imprimé |
| Auteurs : |
A. MUNNICH, Auteur ; Caroline DEMILY, Auteur ; L. FRUGERE, Auteur ; C. DUWIME, Auteur ; V. MALAN, Auteur ; Giulia BARCIA, Auteur ; C. VIDAL, Auteur ; E. THROO, Auteur ; C. BESMOND, Auteur ; L. HUBERT, Auteur ; G. ROLAND-MANUEL, Auteur ; J. P. MALEN, Auteur ; M. FERRERI, Auteur ; S. HANEIN, Auteur ; J. C. THALABARD, Auteur ; Nathalie BODDAERT, Auteur ; Moïse ASSOULINE, Auteur |
| Article en page(s) : |
33 p. |
| Langues : |
Anglais (eng) |
| Mots-clés : |
Autism spectrum disorder Copy number variant Fragile X syndrome Gene panel Genetic counseling Genetic diagnosis Microarray Next-generation sequencing Sequence variant |
| Index. décimale : |
PER Périodiques |
| Résumé : |
Background: Neurogenetics investigations and diagnostic yield in patients with autism spectrum disorder (ASD) have significantly improved over the last few years. Yet, many patients still fail to be systematically investigated. Methods: To improve access to services, an ambulatory team has been established since 1998, delivering on-site clinical genetics consultations and gradually upgrading services to 502 children and young adults with ASD in their standard environment across 26 day-care hospitals and specialized institutions within the Greater Paris region. The evaluation included a clinical genetics consultation, screening for fragile X syndrome, metabolic workup, chromosomal microarray analysis, and, in a proportion of patients, next-generation sequencing of genes reported in ASD and other neurodevelopmental disorders. Results: Fragile X syndrome and pathogenic copy number variants (CNVs) accounted for the disease in 10% of cases, including 4/312 (1.3%) with fragile X syndrome and 34/388 (8.8%) with pathogenic CNVs (19 de novo and 4 inherited). Importantly, adding high-throughput resequencing of reported intellectual disability/ASD genes to the screening procedure had a major impact on diagnostic yield in the 141 patients examined most recently. Pathogenic or likely pathogenic sequence variants in 27 disease genes were identified in 33/141 patients (23.4%; 23 were de novo and 10 inherited, including five X-linked and five recessive compound heterozygous variants). Diagnosed cases presented atypical and/or syndromic ASD with moderate to severe intellectual disability. The diagnostic yield of fragile X syndrome and array CGH testing combined with next-generation sequencing was significantly higher than fragile X syndrome and array CGH alone (p value 0.009). No inborn errors of metabolism were detected with the metabolic screening. Conclusion: Based on the diagnostic rate observed in this cohort, we suggest that a stepwise procedure be considered, first screening pathogenic CNVs and a limited number of disease genes in a much larger number of patients, especially those with syndromic ASD and intellectual disability. |
| En ligne : |
https://dx.doi.org/10.1186/s13229-019-0284-2 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408 |
in Molecular Autism > 10 (2019) . - 33 p.
[article] Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder [texte imprimé] / A. MUNNICH, Auteur ; Caroline DEMILY, Auteur ; L. FRUGERE, Auteur ; C. DUWIME, Auteur ; V. MALAN, Auteur ; Giulia BARCIA, Auteur ; C. VIDAL, Auteur ; E. THROO, Auteur ; C. BESMOND, Auteur ; L. HUBERT, Auteur ; G. ROLAND-MANUEL, Auteur ; J. P. MALEN, Auteur ; M. FERRERI, Auteur ; S. HANEIN, Auteur ; J. C. THALABARD, Auteur ; Nathalie BODDAERT, Auteur ; Moïse ASSOULINE, Auteur . - 33 p. Langues : Anglais ( eng) in Molecular Autism > 10 (2019) . - 33 p.
| Mots-clés : |
Autism spectrum disorder Copy number variant Fragile X syndrome Gene panel Genetic counseling Genetic diagnosis Microarray Next-generation sequencing Sequence variant |
| Index. décimale : |
PER Périodiques |
| Résumé : |
Background: Neurogenetics investigations and diagnostic yield in patients with autism spectrum disorder (ASD) have significantly improved over the last few years. Yet, many patients still fail to be systematically investigated. Methods: To improve access to services, an ambulatory team has been established since 1998, delivering on-site clinical genetics consultations and gradually upgrading services to 502 children and young adults with ASD in their standard environment across 26 day-care hospitals and specialized institutions within the Greater Paris region. The evaluation included a clinical genetics consultation, screening for fragile X syndrome, metabolic workup, chromosomal microarray analysis, and, in a proportion of patients, next-generation sequencing of genes reported in ASD and other neurodevelopmental disorders. Results: Fragile X syndrome and pathogenic copy number variants (CNVs) accounted for the disease in 10% of cases, including 4/312 (1.3%) with fragile X syndrome and 34/388 (8.8%) with pathogenic CNVs (19 de novo and 4 inherited). Importantly, adding high-throughput resequencing of reported intellectual disability/ASD genes to the screening procedure had a major impact on diagnostic yield in the 141 patients examined most recently. Pathogenic or likely pathogenic sequence variants in 27 disease genes were identified in 33/141 patients (23.4%; 23 were de novo and 10 inherited, including five X-linked and five recessive compound heterozygous variants). Diagnosed cases presented atypical and/or syndromic ASD with moderate to severe intellectual disability. The diagnostic yield of fragile X syndrome and array CGH testing combined with next-generation sequencing was significantly higher than fragile X syndrome and array CGH alone (p value 0.009). No inborn errors of metabolism were detected with the metabolic screening. Conclusion: Based on the diagnostic rate observed in this cohort, we suggest that a stepwise procedure be considered, first screening pathogenic CNVs and a limited number of disease genes in a much larger number of patients, especially those with syndromic ASD and intellectual disability. |
| En ligne : |
https://dx.doi.org/10.1186/s13229-019-0284-2 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408 |
|  |
Faire une suggestion Affiner la rechercheImpact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder / A. MUNNICH in Molecular Autism, 10 (2019)
