Aperçu: G.M.
Le trouble du spectre de l'autisme (TSA) est doté d'estimations d'héritabilité impressionnantes et de taux de récidive élevés. Ses
fondements génétiques sont néanmoins très hétérogènes, avec des
variantes communes et rares qui contribuent à des centaines de loci
différents, chacun caractérisé par des niveaux variables de pénétrance. Les
familles multiplex d'un seul groupe ethnique représentent un moyen
utile de réduire l'hétérogénéité et d'améliorer la charge génétique.Ces
résultats fournissent des preuves supplémentaires de l'hétérogénéité
génétique dans les TSA, même dans les familles multiplex appartenant à
un seul groupe ethnique. Les
différences dans la charge de la VCN peuvent probablement contribuer à
l'hétérogénéité clinique importante observée entre frères et sœurs
affectés
Am J Med Genet B Neuropsychiatr Genet. 2017 Mar 17. doi: 10.1002/ajmg.b.32537.
Copy number variation in 19 Italian multiplex families with autism spectrum disorder: Importance of synaptic and neurite elongation genes
Lintas C1, Picinelli C2, Piras IS2, Sacco R1, Brogna C1, Persico AM2,3.
Author information
- 1
- Service for Neurodevelopmental Disorders and Laboratory of Molecular Psychiatry and Neurogenetics, University "Campus Bio-Medico", Rome, Italy.
- 2
- Mafalda Luce Center for Pervasive Developmental Disorders, Milan, Italy.
- 3
- Unit of Child and Adolescent Neuropsychiatry, "Gaetano Martino" University Hospital, University of Messina, Messina, Italy.
Abstract
Autism
Spectrum Disorder (ASD) is endowed with impressive heritability
estimates and high recurrence rates. Its genetic underpinnings are
nonetheless very heterogeneous, with common, and rare contributing
variants located in hundreds of different loci, each characterized by
variable levels of penetrance. Multiplex families from single ethnic
groups represent a useful means to reduce heterogeneity and enhance
genetic load. We screened 19 Italian ASD multiplex families (3 triplets
and 16 duplets, total N = 41 ASD subjects), using array-CGH (Agilent
180 K). Causal or ASD-relevant CNVs were detected in 36.6% (15/41) of
ASD probands, corresponding to 36.8% (7/19) multiplex families with at
least one affected sibling genetically positive. However, only in less
than half (3/7) of positive families, affected siblings share the same
causal or ASD-relevant CNV. Even in these three families, additional
potentially relevant CNVs not shared by affected sib pairs were also
detected. These results provide further evidence of genetic
heterogeneity in ASD even within multiplex families belonging to a
single ethnic group. Differences in CNV burden may likely contribute to
the substantial clinical heterogeneity observed between affected
siblings. In addition, Gene Ontology enrichment analysis indicates that
most potentially causal or relevant ASD genes detected in our cohort
belong to nervous system-specific categories, especially involved in
neurite elongation and synaptic structure/function. These findings point
toward the existence of genomic instability in these families, whose
underlying genetic and epigenetic mechanisms deserve further scrutiny.
© 2017 Wiley Periodicals, Inc.
- PMID: 28304131
- DOI: 10.1002/ajmg.b.32537
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