1. The Number of Genomic Copies at the 16p11.2 Locus Modulates Language, Verbal Memory, and Inhibition
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Jacques S. Beckmann, Martine Doco-Fenzy, Mandy Barker, Alexandre Reymond, Borja Rodriguez-Herreros, Raphael Bernier, Katrin Männik, Andres Metspalu, Loyse Hippolyte, Marion Gérard, Anne M. Maillard, Bogdan Draganski, Anu Reigo, Laurent Mottron, Laurence Schneider, Philippe Conus, Cédric Le Caignec, Sandra Martin-Brevet, Carina Ferrari, Anneli Kolk, Aurélie Pain, Robin P. Goin-Kochel, Nouchine Hadjikhani, Boris Keren, Ellen Hanson, Cyril Mignot, Franck Ramus, Lee Anne Green Snyder, Sébastien Jacquemont, Aurélien Macé, Albert David, Bertrand Isidor, 16p11.2 European Consortium, Simons Variation in Individuals Project Consortium, 16p11.2 European Consortium, and Simons Variation in Individuals Project Consortium
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Adult ,Male ,0301 basic medicine ,Heterozygote ,Adolescent ,DNA Copy Number Variations ,Intelligence ,Chromosome Disorders ,Locus (genetics) ,ASD ,Executive Function ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Memory ,Intellectual Disability ,Chromosome Duplication ,mental disorders ,medicine ,Humans ,Cognitive Dysfunction ,Copy-number variation ,Autistic Disorder ,Child ,Biological Psychiatry ,Inhibition ,Language ,Genetics ,Working memory ,Copy number variation ,Neuropsychology ,Cognition ,Middle Aged ,medicine.disease ,16p11.2 ,Pedigree ,Autistic Disorder/diagnostic imaging ,Autistic Disorder/genetics ,Autistic Disorder/physiopathology ,Child, Preschool ,Chromosome Deletion ,Chromosome Disorders/diagnostic imaging ,Chromosome Disorders/genetics ,Chromosome Disorders/physiopathology ,Chromosome Duplication/genetics ,Chromosomes, Human, Pair 16/genetics ,Cognitive Dysfunction/diagnostic imaging ,Cognitive Dysfunction/genetics ,Cognitive Dysfunction/physiopathology ,DNA Copy Number Variations/genetics ,Executive Function/physiology ,Female ,Intellectual Disability/diagnostic imaging ,Intellectual Disability/genetics ,Intellectual Disability/physiopathology ,Intelligence/genetics ,Memory/physiology ,Motor Skills/physiology ,030104 developmental biology ,Motor Skills ,Autism spectrum disorder ,Autism ,Verbal memory ,Psychology ,Chromosomes, Human, Pair 16 ,030217 neurology & neurosurgery - Abstract
BACKGROUND: Deletions and duplications of the 16p11.2 BP4-BP5 locus are prevalent copy number variations (CNVs), highly associated with autism spectrum disorder and schizophrenia. Beyond language and global cognition, neuropsychological assessments of these two CNVs have not yet been reported. METHODS: This study investigates the relationship between the number of genomic copies at the 16p11.2 locus and cognitive domains assessed in 62 deletion carriers, 44 duplication carriers, and 71 intrafamilial control subjects. RESULTS: IQ is decreased in deletion and duplication carriers, but we demonstrate contrasting cognitive profiles in these reciprocal CNVs. Deletion carriers present with severe impairments of phonology and of inhibition skills beyond what is expected for their IQ level. In contrast, for verbal memory and phonology, the data may suggest that duplication carriers outperform intrafamilial control subjects with the same IQ level. This finding is reminiscent of special isolated skills as well as contrasting language performance observed in autism spectrum disorder. Some domains, such as visuospatial and working memory, are unaffected by the 16p11.2 locus beyond the effect of decreased IQ. Neuroimaging analyses reveal that measures of inhibition covary with neuroanatomic structures previously identified as sensitive to 16p11.2 CNVs. CONCLUSIONS: The simultaneous study of reciprocal CNVs suggests that the 16p11.2 genomic locus modulates specific cognitive skills according to the number of genomic copies. Further research is warranted to replicate these findings and elucidate the molecular mechanisms modulating these cognitive performances.
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