Biomedical subjects

Anthony J Bailey

Publications and source records attributed to Anthony J Bailey.

8 recordsLinked to original sources

PubMed2006

Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection.

Neuroligin abnormalities have been recently implicated in the aetiology of autism spectrum disorders (ASD), given the finding of point mutations in the two X-linked genes NLGN3 and NLGN4X and the important role of neuroligins in synaptogenesis. To enquire on the relevance and frequency of neuroligin mutations in ASD, we performed a mutation screening of NLGN3 and NLGN4X in a sample of 124 autism probands from the International Molecular Genetic Study of Autism Consortium (IMGSAC). We identified a new non-synonymous variant in NLGN3 (Thr632Ala), which is likely to be a rare polymorphism. Our data indicate that coding mutations in these genes are very rarely associated to ASD.

Autistic Disorder↗

PubMed2006

SLC25A12 and CMYA3 gene variants are not associated with autism in the IMGSAC multiplex family sample.

Autism is a severe neurodevelopmental disorder with a complex genetic predisposition. Linkage findings from several genome scans suggest the presence of an autism susceptibility locus on chromosome 2q24-q33, making this region the focus of candidate gene and association studies. Recently, significant association with autism has been reported for single-nucleotide polymorphisms (SNPs) in the SLC25A12 and CMYA3 genes on chromosome 2q. We attempted to replicate these findings in the collection of families from the International Molecular Genetic Study of Autism Consortium (IMGSAC), using the transmission disequilibrium test and case-control comparison. Our study failed to reveal any significant association for the SNPs tested at either locus, suggesting that these variants are unlikely to play a major role in genetic susceptibility to autism in our sample.

Autistic Disorder↗

PubMed2006

Face and gaze processing in normally developing children: a magnetoencephalographic study.

Magnetoencephalography (MEG) was used to study the neural mechanisms underlying face and gaze processing in ten normally developing boys aged between 8 and 11 years and 12 adult males. The participants performed two tasks in which they had to decide whether images presented sequentially in pairs, depicted the same person or the same motorbike. In the first task, the participants saw pictures of faces in which the eyes were either open or shut and pictures of motorbikes. In the second task, participants saw pairs of faces with gaze averted to the left or right. In children there was no evidence of the face sensitive, low amplitude short latency (30-60 ms) activity seen previously in adults. A strong, midline posterior response at approximately 100 ms was observed in children, which was earlier and somewhat stronger to faces than to motorbikes; in adults the signal at this latency was weak. A clear face sensitive response was seen in adults at 135 ms, predominantly over the right inferior occipito-temporal regions. Although activity was observed in the children at the same latency, it was less prominent, not lateralized and was evoked similarly by faces and motorbikes. Averted gaze conditions evoked strong right-lateralized activity at approximately 245 ms in children only. These findings indicate that even in middle childhood the neural mechanisms underlying face processing are less specialized than in adults, with greater early activation of posterior occipital cortices and less specific activation of ventral occipito-temporal cortex.

Adult↗

PubMed2006

Face- and gaze-sensitive neural responses in children with autism: a magnetoencephalographic study.

Face and gaze processing were studied using magnetoencephalography in 10 children with autism and 10 normally developing children, aged between 7 and 12 years. The children performed two tasks in which they had to discriminate whether images of faces presented sequentially in pairs were identical. The images showed four different categories of gaze: direct gaze, eyes averted (left or right) and closed eyes but there was no instruction to focus on the direction of gaze. Images of motorbikes were used as control stimuli. Faces evoked strong activity over posterior brain regions at about 100 ms in both groups of children. A response at 140 ms to faces observed over extrastriate cortices, thought to be homologous to the N170 in adults, was weak and bilateral in both groups and somewhat weaker (approaching significance) in the children with autism than in the control children. The response to motorbikes differed between the groups at 100 and 140 ms. Averted eyes evoked a strong right lateralized component at 240 ms in the normally developing children that was weak in the clinical group. By contrast, direct gaze evoked a left lateralized component at 240 ms only in children with autism. The findings suggest that face and gaze processing in children with autism follows a trajectory somewhat similar to that seen in normal development but with subtle differences. There is also a possibility that other categories of object may be processed in an unusual way. The inter-relationships between these findings remain to be elucidated.

Autistic Disorder↗

PubMed2005

Candidate-gene screening and association analysis at the autism-susceptibility locus on chromosome 16p: evidence of association at GRIN2A and ABAT.

Autism is a highly heritable neurodevelopmental disorder whose underlying genetic causes have yet to be identified. To date, there have been eight genome screens for autism, two of which identified a putative susceptibility locus on chromosome 16p. In the present study, 10 positional candidate genes that map to 16p11-13 were examined for coding variants: A2BP1, ABAT, BFAR, CREBBP, EMP2, GRIN2A, MRTF-B, SSTR5, TBX6, and UBN1. Screening of all coding and regulatory regions by denaturing high-performance liquid chromatography identified seven nonsynonymous changes. Five of these mutations were found to cosegregate with autism, but the mutations are not predicted to have deleterious effects on protein structure and are unlikely to represent significant etiological variants. Selected variants from candidate genes were genotyped in the entire International Molecular Genetics Study of Autism Consortium collection of 239 multiplex families and were tested for association with autism by use of the pedigree disequilibrium test. Additionally, genotype frequencies were compared between 239 unrelated affected individuals and 192 controls. Patterns of linkage disequilibrium were investigated, and the transmission of haplotypes across candidate genes was tested for association. Evidence of single-marker association was found for variants in ABAT, CREBBP, and GRIN2A. Within these genes, 12 single-nucleotide polymorphisms (SNPs) were subsequently genotyped in 91 autism trios (one affected individual and two unaffected parents), and the association was replicated within GRIN2A (Fisher's exact test, P<.0001). Logistic regression analysis of SNP data across GRIN2A and ABAT showed a trend toward haplotypic differences between cases and controls.

4-Aminobutyrate Transaminase↗

PubMed2005

Mutation screening and association analysis of six candidate genes for autism on chromosome 7q.

Genetic studies have provided evidence for an autism susceptibility locus (AUTS1) on chromosome 7q. Screening for mutations in six genes mapping to 7q, CUTL1, SRPK2, SYPL, LAMB1, NRCAM and PTPRZ1 in 48 unrelated individuals with autism led to the identification of several new coding variants in the genes CUTL1, LAMB1 and PTPRZ1. Analysis of genetic variants provided evidence for association with autism for one of the new missense changes identified in LAMB1; this effect was stronger in a subgroup of affected male sibling pair families, implying a possible specific sex-related effect for this variant. Association was also detected for several polymorphisms in the promoter and untranslated region of NRCAM, suggesting that alterations in expression of this gene may be linked to autism susceptibility.

Autistic Disorder↗

PubMed2005

Abnormal activation of face processing systems at early and intermediate latency in individuals with autism spectrum disorder: a magnetoencephalographic study.

The neurological basis of developmental psychopathology in autism is a matter of intense debate. Magnetoencephalography (MEG) was used to study the neuronal responses associated with the processing of faces in 12 able adults with autism spectrum disorders (ASD), performing image categorization and image identification tasks. The neuromagnetic data were analysed using nonparametric time-series analysis and equivalent current dipole estimation. Comparison data were obtained from 22 normally developing adults. In individuals with ASD, the neural responses to images of faces, observed in right extrastriate cortices at approximately 145 ms after stimulus onset, were significantly weaker, less lateralized and less affected by stimulus repetition than in control subjects. Early latency (30-60 ms) responses to face images, over right anterior temporal regions, differed significantly between the two subject groups in the image identification task. No such difference was observed for images of mugs or meaningless geometrical patterns. These findings suggest that, during the course of development in individuals with ASD, the cortical activity associated with the processing of human faces assumes a different-from-normal localization in extrastriate brain regions. This abnormal localization may be associated with unusual, but nevertheless face-specific, fast processing pathways.

Adult↗

PubMed2002

Autism: in search of susceptibility genes.

Autism is a neurodevelopmental disorder of unknown etiology. There is convincing data for the involvement of genetic factors in the development of autism, and the absence of any consistent evidence for an environmental, neuroanatomical, or biochemical cause has led to an increasing number of genetic studies to determine the basis of this complex disorder. The results of recent genetic linkage and candidate gene studies are reviewed in relation to the challenge of clinical and genetic heterogeneity, and prospects for the future of genetic research in autism are considered.

Autistic Disorder↗