1. Awadalla P, Gauthier J, Myers RA, Casals F, Hamdan FF, Griffing AR, Cote M, Henrion E, Spiegelman D, Tarabeux J, Piton A, Yang Y, Boyko A, Bustamante C, Xiong L, Rapoport JL, Addington AM, Delisi JL, Krebs MO, Joober R, Millet B, Fombonne E, Mottron L, Zilversmit M, Keebler J, Daoud H, Marineau C, Roy-Gagnon MH, Dube MP, Eyre-Walker A, Drapeau P, Stone EA, Lafreniere RG, Rouleau GA. {{Direct measure of the de novo mutation rate in autism and schizophrenia cohorts}}. {Am J Hum Genet} (Sep 10);87(3):316-324.
The role of de novo mutations (DNMs) in common diseases remains largely unknown. Nonetheless, the rate of de novo deleterious mutations and the strength of selection against de novo mutations are critical to understanding the genetic architecture of a disease. Discovery of high-impact DNMs requires substantial high-resolution interrogation of partial or complete genomes of families via resequencing. We hypothesized that deleterious DNMs may play a role in cases of autism spectrum disorders (ASD) and schizophrenia (SCZ), two etiologically heterogeneous disorders with significantly reduced reproductive fitness. We present a direct measure of the de novo mutation rate (mu) and selective constraints from DNMs estimated from a deep resequencing data set generated from a large cohort of ASD and SCZ cases (n = 285) and population control individuals (n = 285) with available parental DNA. A survey of approximately 430 Mb of DNA from 401 synapse-expressed genes across all cases and 25 Mb of DNA in controls found 28 candidate DNMs, 13 of which were cell line artifacts. Our calculated direct neutral mutation rate (1.36 x 10(-8)) is similar to previous indirect estimates, but we observed a significant excess of potentially deleterious DNMs in ASD and SCZ individuals. Our results emphasize the importance of DNMs as genetic mechanisms in ASD and SCZ and the limitations of using DNA from archived cell lines to identify functional variants.
2. Gomot M, Blanc R, Clery H, Roux S, Barthelemy C, Bruneau N. {{Candidate Electrophysiological Endophenotypes of Hyper-Reactivity to Change in Autism}}. {J Autism Dev Disord} (Sep 9)
3. Marui T, Funatogawa I, Koishi S, Yamamoto K, Matsumoto H, Hashimoto O, Jinde S, Nishida H, Sugiyama T, Kasai K, Watanabe K, Kano Y, Kato N. {{The NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene variants are associated with autism}}. {Acta Psychiatr Scand} (Sep 5)
Marui T, Funatogawa I, Koishi S, Yamamoto K, Matsumoto H, Hashimoto O, Jinde S, Nishida H, Sugiyama T, Kasai K, Watanabe K, Kano Y, Kato N. The NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene variants are associated with autism. Objective: Autism appears to have a strong genetic component. The product of the NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene is included in the mitochondrial electron transport chain. Method: We performed a case-control study of 235 patients with autism and 214 controls and examined three single-nucleotide polymorphisms (SNPs) within this gene in a Japanese population. We then conducted a transmission disequilibrium test (TDT) analysis in 148 autistic trios. Results: In the case-control study, two SNPs (rs12666974 and rs3779262) showed a significant association with autism (P = 0.00064 and 0.00046 respectively). Furthermore, a haplotype containing these two SNPs showed a significant association (P-global = 0.0013, individual haplotype A-A: P = 0.010). In TDT analysis, the global and A-A haplotype P-values also indicated significant associations. Minor allele and genotype frequencies were decreased in the autistic subjects. Conclusion: We found significant association between the NDFA5 gene and autism.
4. Weiss JA, Lunsky Y. {{Group cognitive behaviour therapy for adults with Asperger syndrome and anxiety or mood disorder: a case series}}. {Clin Psychol Psychother} (Sep);17(5):438-446.
Individuals with Asperger syndrome are at increased risk for mental health problems compared with the general population, especially with regard to mood and anxiety disorders. Generic mental health services are often ill-equipped to offer psychotherapeutic treatments to this population, and specialized supports are difficult to find. This case series used a manualized cognitive behaviour therapy group programme (Mind Over Mood) with three adults diagnosed with Asperger syndrome, who were each unable to access psychotherapy through mainstream mental health services. This review highlights the benefits of a cognitive behaviour therapy (CBT) group approach for adults with Asperger syndrome and suggests some potential modifications to traditional CBT provision. Copyright (c) 2010 John Wiley & Sons, Ltd.Key Practitioner Message:* As a group, adults with Asperger syndrome are at high risk for anxiety disorders and depression.* Cognitive behaviour therapy can be adapted to help adults with Asperger syndrome cope with anxiety or depression.* Group cognitive behaviour therapy for adults with Asperger syndrome may hold a number of advantages to individual therapy.
5. Yasuhara A. {{Correlation between EEG abnormalities and symptoms of autism spectrum disorder (ASD)}}. {Brain Dev} (Sep 6)
Children with ASD often suffer from epilepsy and paroxysmal EEG abnormality. Purposes of this study are the confirmation of incidence of epileptic seizures and EEG abnormalities in children with autism using a high performance digital EEG, to examine the nature of EEG abnormalities such as locus or modality, and to determine if the development of children with ASD, who have experienced developmental delay, improves when their epilepsy has been treated and maintained under control. A total of 1014 autistic children that have been treated and followed-up for more than 3 years at Yasuhara Children’s Clinic in Osaka, Japan, were included in this study. Each participant’s EEG had been recorded approximately every 6 months under sleep conditions. Epilepsy was diagnosed in 37% (375/1014) of the study participants. Almost all patients diagnosed with epilepsy presented with symptomatic epilepsy. The data showed that the participants with lower IQ had a higher incidence of epileptic seizures. Epileptic EEG discharges occurred in 85.8% (870/1014) of the patients. There was also a very high incidence of spike discharges in participants whose intellectual quotient was very low or low. Epileptic seizure waves most frequently developed from the frontal lobe (65.6%), including the front pole (Fp1 and Fp2), frontal part (F3, F4, F7 and F8) and central part (C3, Cz and C4). The occurrence rate of spike discharges in other locations, including temporal lobe (T3, T4, T5, T6), parietal lobe (P3, Pz, P4), occipital lobe (O1, O2) and multifocal spikes was less than 10%. These results support the notion that there is a relationship between ASD and dysfunction of the mirror neuron system. The management of seizure waves in children diagnosed with ASD may result in improves function and reduction of autistic symptoms.
