title: The Number of Genomic Copies at the 16p11.2 Locus Modulates Language, Verbal Memory, and Inhibition.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Service de Génétique Médicale, University of Lausanne, Lausanne, Switzerland.
authors.forename: Loyse
authors.initials: L
authors.lastname: Hippolyte
authors.affiliation: Service de Génétique Médicale, University of Lausanne, Lausanne, Switzerland.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Maillard
authors.affiliation: Service de Génétique Médicale, University of Lausanne, Lausanne, Switzerland; LREN-Département des Neurosciences Cliniques, University of Lausanne, Lausanne, Switzerland.
authors.forename: Borja
authors.initials: B
authors.lastname: Rodriguez-Herreros
authors.affiliation: Service de Génétique Médicale, University of Lausanne, Lausanne, Switzerland.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Pain
authors.affiliation: Service de Génétique Médicale, University of Lausanne, Lausanne, Switzerland; LREN-Département des Neurosciences Cliniques, University of Lausanne, Lausanne, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Martin-Brevet
authors.affiliation: Department of Psychiatry, University of Lausanne, Lausanne, Switzerland.
authors.forename: Carina
authors.initials: C
authors.lastname: Ferrari
authors.affiliation: Department of Psychiatry, University of Lausanne, Lausanne, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Conus
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland; SIB Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Macé
authors.affiliation: Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Nouchine
authors.initials: N
authors.lastname: Hadjikhani
authors.affiliation: Department of Genetics, Tartu University Hospital, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.affiliation: Department of Genetics, Tartu University Hospital, Tartu, Estonia.
authors.forename: Anu
authors.initials: A
authors.lastname: Reigo
authors.affiliation: United Laboratories, and Children's Clinic, Department of Neurology and Neurorehabilitation, Tartu University Hospital, Tartu, Estonia.
authors.forename: Anneli
authors.initials: A
authors.lastname: Kolk
authors.affiliation: Center for Integrative Genomics, University of Lausanne;Lausanne, Switzerland; Department of Genetics, Tartu University Hospital, Tartu, Estonia.
authors.forename: Katrin
authors.initials: K
authors.lastname: Männik
authors.affiliation: CERY Hospital, Department of Child Psychiatry, University of Lausanne, Lausanne, Switzerland.
authors.forename: Mandy
authors.initials: M
authors.lastname: Barker
authors.affiliation: Service de Génétique Médicale, CHU-Nantes, Nantes.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Isidor
authors.affiliation: Service de Génétique Médicale, CHU-Nantes, Nantes; Inserm UMR957, Faculté de Médecine, Nantes.
authors.forename: Cédric
authors.initials: C
authors.lastname: Le Caignec
authors.affiliation: Department of Genetics and Cytogenetics, Unité fonctionnelle de génétique clinique, Groupe Hospitalier Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France; Centre de Référence "Déficiences intellectuelles de causes rares" and Groupe de Recherche Clinique "Déficience intellectuelle et autisme", UPMC, Paris, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Mignot
authors.affiliation: SUPEA, and Service of Neuropsychology and Neurorehabilitation, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Laurence
authors.initials: L
authors.lastname: Schneider
authors.affiliation: Département de Psychiatrie, Université de Montréal and Hôpital Rivière des Prairies, Montreal, Quebec, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Mottron
authors.affiliation: Department of Genetics and Cytogenetics, Unité fonctionnelle de génétique clinique, Groupe Hospitalier Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Boris
authors.initials: B
authors.lastname: Keren
authors.affiliation: Service de Génétique Médicale, CHU-Nantes, Nantes.
authors.forename: Albert
authors.initials: A
authors.lastname: David
authors.affiliation: Service de Génétique, CHU, Reims.
authors.forename: Martine
authors.initials: M
authors.lastname: Doco-Fenzy
authors.affiliation: Department of Genetics and Cytogenetics, Unité fonctionnelle de génétique clinique, Groupe Hospitalier Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France; Département de Génétique, Hôpital Robert Debré, Université Paris VII-Paris Diderot, Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Gérard
authors.affiliation: Department of Psychiatry and Behavioral Science, University of Washington, Seattle, Washington.
authors.forename: Raphael
authors.initials: R
authors.lastname: Bernier
authors.affiliation: Department of Pediatrics, Psychology Section, Baylor College of Medicine, Houston, Texas.
authors.forename: Robin P
authors.initials: RP
authors.lastname: Goin-Kochel
authors.affiliation: Department of Psychiatry, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ellen
authors.initials: E
authors.lastname: Hanson
authors.affiliation: Clinical Research Associates, New York, New York.
authors.forename: LeeAnne
authors.initials: L
authors.lastname: Green Snyder
authors.affiliation: Laboratoire de Sciences Cognitives et Psycholinguistique, Département d'Etudes Cognitives, Ecole Normale Supérieure, EHESS, CNRS, PSL Research University, Paris, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Ramus
authors.affiliation: Service de Génétique Médicale, University of Lausanne, Lausanne, Switzerland; SIB Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Beckmann
authors.affiliation: LREN-Département des Neurosciences Cliniques, University of Lausanne, Lausanne, Switzerland; Department of Neurology (BD), Max-Planck Institute for Human Cognitive and Brain Science, Leipzig, Germany.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Draganski
authors.affiliation: Center for Integrative Genomics, University of Lausanne;Lausanne, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Reymond
authors.affiliation: Service de Génétique Médicale, University of Lausanne, Lausanne, Switzerland. Electronic address: sebastien.jacquemont@umontreal.ca.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Jacquemont
mesh_terms: D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D058674:Chromosome Duplication / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D056915:DNA Copy Number Variations / Q000235:genetics*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008607:Intellectual Disability / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D007360:Intelligence / Q000235:genetics*; D007802:Language; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D009048:Motor Skills / Q000502:physiology*; D010375:Pedigree; D055815:Young Adult
keywords: 16p11.2; ASD; Copy number variation; Inhibition; Language; Memory