Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2.
Détails
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_D332BE38D258
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2.
Périodique
NeuroImage
ISSN
1095-9572 (Electronic)
ISSN-L
1053-8119
Statut éditorial
Publié
Date de publication
15/11/2010
Peer-reviewed
Oui
Volume
53
Numéro
3
Pages
1030-1042
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Recent genetic studies have implicated a number of candidate genes in the pathogenesis of Autism Spectrum Disorder (ASD). Polymorphisms of CNTNAP2 (contactin-associated like protein-2), a member of the neurexin family, have already been implicated as a susceptibility gene for autism by at least 3 separate studies. We investigated variation in white and grey matter morphology using structural MRI and diffusion tensor imaging. We compared volumetric differences in white and grey matter and fractional anisotropy values in control subjects characterised by genotype at rs7794745, a single nucleotide polymorphism in CNTNAP2. Homozygotes for the risk allele showed significant reductions in grey and white matter volume and fractional anisotropy in several regions that have already been implicated in ASD, including the cerebellum, fusiform gyrus, occipital and frontal cortices. Male homozygotes for the risk alleles showed greater reductions in grey matter in the right frontal pole and in FA in the right rostral fronto-occipital fasciculus compared to their female counterparts who showed greater reductions in FA of the anterior thalamic radiation. Thus a risk allele for autism results in significant cerebral morphological variation, despite the absence of overt symptoms or behavioural abnormalities. The results are consistent with accumulating evidence of CNTNAP2's function in neuronal development. The finding suggests the possibility that the heterogeneous manifestations of ASD can be aetiologically characterised into distinct subtypes through genetic-morphological analysis.
Mots-clé
Anisotropy, Cerebellum/pathology, Child, Child Development Disorders, Pervasive/genetics, Child Development Disorders, Pervasive/physiopathology, Endophenotypes, Female, Frontal Lobe/pathology, Genetic Predisposition to Disease, Genotype, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging/methods, Male, Membrane Proteins/genetics, Nerve Tissue Proteins/genetics, Neural Pathways/pathology, Occipital Lobe/pathology, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Polymorphism, Single Nucleotide
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/10/2010 14:28
Dernière modification de la notice
19/12/2023 8:27