pubmed: autism and genetics

Subscribe to pubmed: autism and genetics feed pubmed: autism and genetics
NCBI: db=pubmed; Term=autism AND genetics
Updated: 2 hours 12 min ago

Autism spectrum disorder and the cerebellum.

July 16, 2014 - 8:37am
Related Articles

Autism spectrum disorder and the cerebellum.

Int Rev Neurobiol. 2013;113:1-34

Authors: Becker EB, Stoodley CJ

Abstract
The cerebellum has been long known for its importance in motor learning and coordination. Recently, anatomical, clinical, and neuroimaging studies strongly suggest that the cerebellum supports cognitive functions, including language and executive functions, as well as affective regulation. Furthermore, the cerebellum has emerged as one of the key brain regions affected in autism. Here, we discuss our current understanding of the role of the cerebellum in autism, including evidence from genetic, molecular, clinical, behavioral, and neuroimaging studies. Cerebellar findings in autism suggest developmental differences at multiple levels of neural structure and function, indicating that the cerebellum is an important player in the complex neural underpinnings of autism spectrum disorder, with behavioral implications beyond the motor domain.

PMID: 24290381 [PubMed - indexed for MEDLINE]

[Autism and epigenetics. A model of explanation for the understanding of the genesis in autism spectrum disorders].

July 16, 2014 - 8:37am
Related Articles

[Autism and epigenetics. A model of explanation for the understanding of the genesis in autism spectrum disorders].

Medicina (B Aires). 2013;73 Suppl 1:20-9

Authors: Arberas C, Ruggieri V

Abstract
Autism spectrum disorders are characterized by impairment of social integration and language development and restricted interests. Autism spectrum disorders manifest during childhood and may have a varying clinical expression over the years related to different therapeutic approaches, behavior-modifying drugs, and environmental factors, among others. So far, the genetic alterations identified are not sufficient to explain the genesis of all these processes, as many of the mutations found are also present in unaffected individuals. Findings on the underlying biological and pathophysiological mechanisms of entities strongly associated with autism spectrum disorders, such as Rett, fragile X, Angelman, and fetal alcohol syndromes, point to the role of epigenetic changes in disorders of neurodevelopment. Epigenetic phenomena are normal biological processes necessary for cell and thus human life, especially related to embryonic development. Different phenomena that affect epigenetic processes (changes that change operation or expression of a gene, without modifying the DNA structure) have also been shown to be important in the genesis of neurodevelopmental disorders. Alterations in the epigenetic mechanism may be reversible, which may explain the variation in the autism phenotype over time. Here we analyze the normal epigenetic mechanisms, autism spectrum disorders, their association with specific entities associated with altered epigenetic mechanisms, and possible therapeutic approaches targeting these alterations.

PMID: 24072048 [PubMed - indexed for MEDLINE]

Mutations in SLC35A3 cause autism spectrum disorder, epilepsy and arthrogryposis.

July 16, 2014 - 8:37am
Related Articles

Mutations in SLC35A3 cause autism spectrum disorder, epilepsy and arthrogryposis.

J Med Genet. 2013 Nov;50(11):733-9

Authors: Edvardson S, Ashikov A, Jalas C, Sturiale L, Shaag A, Fedick A, Treff NR, Garozzo D, Gerardy-Schahn R, Elpeleg O

Abstract
BACKGROUND: The heritability of autism spectrum disorder is currently estimated at 55%. Identification of the molecular basis of patients with syndromic autism extends our understanding of the pathogenesis of autism in general. The objective of this study was to find the gene mutated in eight patients from a large kindred, who suffered from autism spectrum disorder, arthrogryposis and epilepsy.
METHODS AND RESULTS: By linkage analysis and exome sequencing, we identified deleterious mutations in SLC35A3 in these patients. SLC35A3 encodes the major Golgi uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) transporter. In Golgi vesicles isolated from patient fibroblasts the transport of the respective nucleotide sugar was significantly reduced causing a massive decrease in the content of cell surface expressed highly branched N-glycans and a concomitant sharp increase of lower branched glycoforms.
CONCLUSIONS: Spontaneous mutation in SLC35A3 has been discovered in cattle worldwide, recapitulating the human phenotype with arthrogryposis and additional skeletal defects known as Complex Vertebral Malformation syndrome. The skeletal anomalies in the mutant cattle and in our patients, and perhaps even the neurological symptoms are likely the consequence of the lack of high-branched N-glycans and the concomitant abundance of lower-branched glycoforms at the cell surface. This pattern has previously been associated with growth arrest and induction of differentiation. With this study, we add SLC35A3 to the gene list of autism spectrum disorders, and underscore the crucial importance of UDP-GlcNAc in the regulation of the N-glycan branching pathway in the Golgi apparatus.

PMID: 24031089 [PubMed - indexed for MEDLINE]

ADHD, autism spectrum disorder, temperament, and character: phenotypical associations and etiology in a Swedish childhood twin study.

July 16, 2014 - 8:37am
Related Articles

ADHD, autism spectrum disorder, temperament, and character: phenotypical associations and etiology in a Swedish childhood twin study.

Compr Psychiatry. 2013 Nov;54(8):1140-7

Authors: Kerekes N, Brändström S, Lundström S, Råstam M, Nilsson T, Anckarsäter H

Abstract
OBJECTIVE: To explore the links between neurodevelopmental disorders - attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) - and personality in a population-based, genetically sensitive study of children.
METHOD: A population-based sample of 1886 twins aged 9 and 12, enriched for childhood mental health problems, was recruited from the Child and Adolescent Twin Study in Sweden (CATSS). Parents were interviewed over the telephone using the Autism-Tics, AD/HD and other Comorbidities (A-TAC) inventory, and in a second step they rated their children according to the Junior Temperament and Character Inventory (JTCI).
RESULTS: ADHD was strongly correlated with novelty seeking, while ASD was correlated positively with harm avoidance and negatively with reward dependence. The strongest associations between personality traits and neurodevelopmental disorders were negative correlations between the character dimensions of self-directedness and cooperativeness and ADHD and ASD alike. Cross-twin cross-trait correlations between ADHD, ASD, and personality dimensions in monozygotic twins were more than double those in dizygotic twins, indicating a strong genetic effect behind the phenotypic covariation between neurodevelopmental disorders and personality.
CONCLUSIONS: Neurodevelopmental disorders are linked specifically to particular temperament profiles and generally to hampered development of the self-governing strategies referred to as "character." Poor self-agency and cooperation may be core functional outcomes in the separation of children with handicapping conditions from those with traits only reminiscent of neurodevelopmental disorders. The associations between neurodevelopmental disorders and personality are at least partly due to genetic effects influencing both conditions. As a consequence, personality must be broadly considered in neuropsychiatry, just as neuropsychiatric disorders and their genetic, neurodevelopmental, and cognitive susceptibilities have to be in personality research and clinical treatment.

PMID: 23790516 [PubMed - indexed for MEDLINE]

Disruption of TBC1D7, a subunit of the TSC1-TSC2 protein complex, in intellectual disability and megalencephaly.

July 16, 2014 - 8:37am
Related Articles

Disruption of TBC1D7, a subunit of the TSC1-TSC2 protein complex, in intellectual disability and megalencephaly.

J Med Genet. 2013 Nov;50(11):740-4

Authors: Capo-Chichi JM, Tcherkezian J, Hamdan FF, Décarie JC, Dobrzeniecka S, Patry L, Nadon MA, Mucha BE, Major P, Shevell M, Bencheikh BO, Joober R, Samuels ME, Rouleau GA, Roux PP, Michaud JL

Abstract
BACKGROUND: Mutations in TSC1 or TSC2 cause the tuberous sclerosis complex (TSC), a disorder characterised by the development of hamartomas or benign tumours in various organs as well as the variable presence of epilepsy, intellectual disability (ID) and autism. TSC1, TSC2 and the recently described protein TBC1D7 form a complex that inhibits mTORC1 signalling and limits cell growth. Although it has been proposed that mutations in TBC1D7 might also cause TSC, loss of its function has not yet been documented in humans.
METHODS AND RESULTS: We used homozygosity mapping and exome sequencing to study a consanguineous family with ID and megalencephaly but without any specific features of TSC. We identified only one rare coding variant, c.538delT:p.Y180fsX1 in TBC1D7, in the regions of homozygosity shared by the affected siblings. We show that this mutation abolishes TBC1D7 expression and is associated with increased mTORC1 signalling in cells of the affected individuals.
CONCLUSIONS: Our study suggests that disruption of TBC1D7 causes ID but without the other typical features found in TSC. Although megalencephaly is not commonly observed in TSC, it has been associated with mTORC1 activation. Our observation thus reinforces the relationship between this pathway and the development of megalencephaly.

PMID: 23687350 [PubMed - indexed for MEDLINE]

Insights into GABAAergic System Deficits in Fragile X Syndrome Lead to Clinical Trials.

July 13, 2014 - 7:11am

Insights into GABAAergic System Deficits in Fragile X Syndrome Lead to Clinical Trials.

Neuropharmacology. 2014 Jul 9;

Authors: Braat S, Kooy RF

Abstract
An increasing number of studies implicate the GABAAergic system in the pathophysiology of the fragile X syndrome, a frequent cause of intellectual disability and autism. Animal models have proven invaluable in unravelling the molecular mechanisms underlying the disorder. Multiple defects in this inhibitory system have been identified in Fmr1 knockout mice, including altered expression of various components, aberrant GABAA receptor-mediated signalling, altered GABA concentrations and anatomical defects in GABAergic neurons. Aberrations compatible with those described in the mouse model were detected in dfmr1 deficient Drosophila melanogaster, a validated fly model for the fragile X syndrome. Treatment with drugs that ameliorate the GABAAergic deficiency in both animal models have demonstrated that the GABAA receptor is a promising target for the treatment of fragile X patients. Based on these preclinical studies, clinical trials in patients have been initiated.

PMID: 25016041 [PubMed - as supplied by publisher]

Neural Signatures of Autism Spectrum Disorders: Insights into Brain Network Dynamics.

July 12, 2014 - 6:22am

Neural Signatures of Autism Spectrum Disorders: Insights into Brain Network Dynamics.

Neuropsychopharmacology. 2014 Jul 11;

Authors: Hernandez LM, Rudie JD, Green SA, Bookheimer S, Dapretto M

Abstract
Neuroimaging investigations of Autism Spectrum Disorders (ASDs) have advanced our understanding of atypical brain function and structure, and have recently converged on a model of altered network-level connectivity. Traditional task-based functional magnetic resonance imaging (MRI) and volume-based structural MRI studies have identified widespread atypicalities in brain regions involved in social behavior and other core ASD-related behavioral deficits. More recent advances in MR-neuroimaging methods allow for quantification of brain connectivity using diffusion tensor imaging, functional connectivity, and graph theoretic methods. These newer techniques have moved the field toward a systems-level understanding of ASD etiology, integrating functional and structural measures across distal brain regions. Neuroimaging findings in ASD as a whole have been mixed and at times contradictory, likely due to the vast genetic and phenotypic heterogeneity characteristic of the disorder. Future longitudinal studies of brain development will be crucial to yield insights into mechanisms of disease etiology in ASD subpopulations. Advances in neuroimaging methods and large-scale collaborations will also allow for an integrated approach linking neuroimaging, genetics, and phenotypic data.Neuropsychopharmacology Reviews accepted article preview online, 11 July 2014; doi:10.1038/npp.2014.172.

PMID: 25011468 [PubMed - as supplied by publisher]

Pages