Autism as a strongly genetic disorder: evidence from a British twin study.
ABSTRACT Two previous epidemiological studies of autistic twins suggested that autism was predominantly genetically determined, although the findings with regard to a broader phenotype of cognitive, and possibly social, abnormalities were contradictory. Obstetric and perinatal hazards were also invoked as environmentally determined aetiological factors. The first British twin sample has been re-examined and a second total population sample of autistic twins recruited. In the combined sample 60% of monozygotic (MZ) pairs were concordant for autism versus no dizygotic (DZ) pairs; 92% of MZ pairs were concordant for a broader spectrum of related cognitive or social abnormalities versus 10% of DZ pairs. The findings indicate that autism is under a high degree of genetic control and suggest the involvement of multiple genetic loci. Obstetric hazards usually appear to be consequences of genetically influenced abnormal development, rather than independent aetiological factors. Few new cases had possible medical aetiologies, refuting claims that recognized disorders are common aetiological influences.
SourceAvailable from: Khaled Saad[Show abstract] [Hide abstract]
ABSTRACT: Objectives: Autism spectrum disorder (ASD) is a developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and nonverbal communication, and stereotyped patterns of interests and activities. Vitamin-D deficiency was previously reported in autistic children. However, the data on the relationship between vitamin D deficiency and the severity of autism is limited. Methods: We performed a case-controlled cross sectional analysis conducted on a 122 ASD children, to assess their vitamin D status compared to controls and the relationship between vitamin D deficiency and the severity of autism. We also conducted an open trial of vitamin D supplementation in ASD children. Results: Fifty-seven % of the patients in the present study had vitamin D deficiency, and thirty % had vitamin D insufficiency. The mean 25-OHD levels in patients with severe autism were significantly lower than those in patients with mild/moderate autism. Serum 25-OHD levels had significant negative correlations with CARS scores. Of the ASD group, 106 patients with low serum 25-OHD levels (<30 ng/ml) participated in the open label trial. They received vitamin D3 (300 IU/Kg/day not to exceed 5,000 IU/day) for three months. Eighty-three subjects completed three months of daily vitamin D treatment. Collectively 80.72% (67/83) of subjects who received vitamin D3 treatment had significantly improved outcome, which was mainly in the sections of the CARS and ABC subscales that measure behavior, stereotypy, eye contact and attention span. Conclusion, vitamin D is inexpensive, readily available and safe. It may have beneficial effects in ASD subjects, especially when the final serum level is more than 40 ng/ml.Nutritional Neuroscience 04/2015; DOI:10.1179/1476830515Y.0000000019 · 2.11 Impact Factor
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ABSTRACT: Autism spectrum disorders (ASDs) are highly heritable and characterised by deficits in social interaction and communication, as well as restricted and repetitive behaviours. Although a number of highly penetrant ASD gene variants have been identified, there is growing evidence to support a causal role for combinatorial effects arising from the contributions of multiple loci. By examining synaptic and circadian neurological phenotypes resulting from the dosage variants of unique human:fly orthologues in Drosophila, we observe numerous synergistic interactions between pairs of informatically-identified candidate genes whose orthologues are jointly affected by large de novo copy number variants (CNVs). These CNVs were found in the genomes of individuals with autism, including a patient carrying a 22q11.2 deletion. We first demonstrate that dosage alterations of the unique Drosophila orthologues of candidate genes from de novo CNVs that harbour only a single candidate gene display neurological defects similar to those previously reported in Drosophila models of ASD-associated variants. We then considered pairwise dosage changes within the set of orthologues of candidate genes that were affected by the same single human de novo CNV. For three of four CNVs with complete orthologous relationships, we observed significant synergistic effects following the simultaneous dosage change of gene pairs drawn from a single CNV. The phenotypic variation observed at the Drosophila synapse that results from these interacting genetic variants supports a concordant phenotypic outcome across all interacting gene pairs following the direction of human gene copy number change. We observe both specificity and transitivity between interactors, both within and between CNV candidate gene sets, supporting shared and distinct genetic aetiologies. We then show that different interactions affect divergent synaptic processes, demonstrating distinct molecular aetiologies. Our study illustrates mechanisms through which synergistic effects resulting from large structural variation can contribute to human disease.PLoS Genetics 02/2015; 11(3):e1004998. DOI:10.1371/journal.pgen.1004998 · 8.17 Impact Factor
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DESCRIPTION: Nachshen, J., Garcin, N., Moxness, K., Tremblay, Y., Hutchinson, P., Lachance, A., Beaurivage, M., Breitenbach, M., Bryson, S., Burack, J., Caron, C., Condillac, R. A., Cornick, A., Ouellette-Kuntz, H., Joseph, S., Rishikof, E., Sladeczek, I. E., Steiman, M., Tidmarsh, L., Zwaigenbaum, L., Fombonne, E., Szatmari, P., Martin-Storey, A., & Ruttle, P.L. (2008). Screening, Assessment, and Diagnosis of Autism Spectrum Disorders in Young Children: Canadian Best Practice Guidelines. Miriam Foundation, Montreal, Quebec.