Titre
A Genetics-First Approach to Dissecting the Heterogeneity of Autism: Phenotypic Comparison of Autism Risk Copy Number Variants.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Chawner, SJRA
Auteure/Auteur
Doherty, J.L.
Auteure/Auteur
Anney, RJL
Auteure/Auteur
Antshel, K.M.
Auteure/Auteur
Bearden, C.E.
Auteure/Auteur
Bernier, R.
Auteure/Auteur
Chung, W.K.
Auteure/Auteur
Clements, C.C.
Auteure/Auteur
Curran, S.R.
Auteure/Auteur
Cuturilo, G.
Auteure/Auteur
Fiksinski, A.M.
Auteure/Auteur
Gallagher, L.
Auteure/Auteur
Goin-Kochel, R.P.
Auteure/Auteur
Gur, R.E.
Auteure/Auteur
Hanson, E.
Auteure/Auteur
Jacquemont, S.
Auteure/Auteur
Kates, W.R.
Auteure/Auteur
Kushan, L.
Auteure/Auteur
Maillard, A.M.
Auteure/Auteur
McDonald-McGinn, D.M.
Auteure/Auteur
Mihaljevic, M.
Auteure/Auteur
Miller, J.S.
Auteure/Auteur
Moss, H.
Auteure/Auteur
Pejovic-Milovancevic, M.
Auteure/Auteur
Schultz, R.T.
Auteure/Auteur
Green-Snyder, L.
Auteure/Auteur
Vorstman, J.A.
Auteure/Auteur
Wenger, T.L.
Auteure/Auteur
Hall, J.
Auteure/Auteur
Owen, M.J.
Auteure/Auteur
van den Bree, MBM
Auteure/Auteur
Contributrices/contributeurs
Baker, K.
Dewhurst, E.
Lafont, A.
Raymond, F.L.
Shirley, T.
Tilley, H.
Timur, H.
Titterton, C.
Walker, N.
Wallwork, S.
Wicks, F.
Ye, Z.
Erwood, M.
Andrews, S.
Birch, P.
Bowen, S.
Bradley, K.
Challenger, A.
Chawner, S.
Cuthbert, A.
Hall, J.
Holmans, P.
Law, S.
Lewis, N.
Morrison, S.
Moss, H.
Owen, M.
Ray, S.
Sopp, M.
Tong, M.
van den Bree, M.
Coscini, N.
Davies, S.
Denaxas, S.
Denyer, H.
Fatih, N.
Juj, M.
Kerry, E.
Lucock, A.
Mandy, W.
Printzlau, F.
Skuse, D.
Srinivasan, R.
Walker, S.
Watkins, A.
Wolstencroft, J.
Searle, B.
Pelling, A.
Dean, J.
Robertson, L.
Williams, D.
Donaldson, A.
Raymond, L.
Procter, A.
Berg, J.
Crow, Y.
Lampe, A.
Rankin, J.
Joss, S.
Chitty, L.
Flinter, F.
Holder, M.
Kraus, A.
Barwell, J.
Vasudevan, P.
Weber, A.
Newman, W.
Splitt, M.
Clowes, V.
van Dijk, F.
Harrison, R.
Kini, U.
Quarrell, O.
Baralle, D.
Mansour, S.
Groupes de travail
IMAGINE-ID Consortium
Liens vers les unités
ISSN
1535-7228
Statut éditorial
Publié
Date de publication
2021-01-01
Volume
178
Numéro
1
Première page
77
Dernière page/numéro d’article
86
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Certain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is underpinned by specific genotype-phenotype relationships.
This international study included 547 individuals (mean age, 12.3 years [SD=4.2], 54% male) who were ascertained on the basis of having a genetic diagnosis of a rare CNV associated with high risk of autism (82 16p11.2 deletion carriers, 50 16p11.2 duplication carriers, 370 22q11.2 deletion carriers, and 45 22q11.2 duplication carriers), as well as 2,027 individuals (mean age, 9.1 years [SD=4.9], 86% male) with autism of heterogeneous etiology. Assessments included the Autism Diagnostic Interview-Revised and IQ testing.
The four genetic variant groups differed in autism symptom severity, autism subdomain profile, and IQ profile. However, substantial variability was observed in phenotypic outcome in individual genetic variant groups (74%-97% of the variance, depending on the trait), whereas variability between groups was low (1%-21%, depending on the trait). CNV carriers who met autism criteria were compared with individuals with heterogeneous autism, and a range of profile differences were identified. When clinical cutoff scores were applied, 54% of individuals with one of the four CNVs who did not meet full autism diagnostic criteria had elevated levels of autistic traits.
Many CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant.
This international study included 547 individuals (mean age, 12.3 years [SD=4.2], 54% male) who were ascertained on the basis of having a genetic diagnosis of a rare CNV associated with high risk of autism (82 16p11.2 deletion carriers, 50 16p11.2 duplication carriers, 370 22q11.2 deletion carriers, and 45 22q11.2 duplication carriers), as well as 2,027 individuals (mean age, 9.1 years [SD=4.9], 86% male) with autism of heterogeneous etiology. Assessments included the Autism Diagnostic Interview-Revised and IQ testing.
The four genetic variant groups differed in autism symptom severity, autism subdomain profile, and IQ profile. However, substantial variability was observed in phenotypic outcome in individual genetic variant groups (74%-97% of the variance, depending on the trait), whereas variability between groups was low (1%-21%, depending on the trait). CNV carriers who met autism criteria were compared with individuals with heterogeneous autism, and a range of profile differences were identified. When clinical cutoff scores were applied, 54% of individuals with one of the four CNVs who did not meet full autism diagnostic criteria had elevated levels of autistic traits.
Many CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant.
PID Serval
serval:BIB_5ECDBFBED24E
PMID
Open Access
Oui
Date de création
2021-01-11T13:27:28.490Z
Date de création dans IRIS
2025-05-20T18:58:20Z