1. Bolte S, Schlitt S, Gapp V, Hainz D, Schirman S, Poustka F, Weber B, Freitag C, Ciaramidaro A, Walter H. {{A Close Eye on the Eagle-Eyed Visual Acuity Hypothesis of Autism}}. {J Autism Dev Disord};2011 (Jun 10)
Autism spectrum disorders (ASD) have been associated with sensory hypersensitivity. A recent study reported visual acuity (VA) in ASD in the region reported for birds of prey. The validity of the results was subsequently doubted. This study examined VA in 34 individuals with ASD, 16 with schizophrenia (SCH), and 26 typically developing (TYP). Participants with ASD did not show higher VA than those with SCH and TYP. There were no substantial correlations of VA with clinical severity in ASD or SCH. This study could not confirm the eagle-eyed acuity hypothesis of ASD, or find evidence for a connection of VA and clinical phenotypes. Research needs to further address the origins and circumstances associated with altered sensory or perceptual processing in ASD.
2. Gilman SR, Iossifov I, Levy D, Ronemus M, Wigler M, Vitkup D. {{Rare de novo variants associated with autism implicate a large functional network of genes involved in formation and function of synapses}}. {Neuron};2011 (Jun 9);70(5):898-907.
Identification of complex molecular networks underlying common human phenotypes is a major challenge of modern genetics. In this study, we develop a method for network-based analysis of genetic associations (NETBAG). We use NETBAG to identify a large biological network of genes affected by rare de novo CNVs in autism. The genes forming the network are primarily related to synapse development, axon targeting, and neuron motility. The identified network is strongly related to genes previously implicated in autism and intellectual disability phenotypes. Our results are also consistent with the hypothesis that significantly stronger functional perturbations are required to trigger the autistic phenotype in females compared to males. Overall, the presented analysis of de novo variants supports the hypothesis that perturbed synaptogenesis is at the heart of autism. More generally, our study provides proof of the principle that networks underlying complex human phenotypes can be identified by a network-based functional analysis of rare genetic variants.
3. Koganti S, Gunarathne A, Desai P, Banerjee P. {{A rare type of ‘coronary arterial – left ventricular fistula’ via thebesian veins in a Fragile X syndrome carrier}}. {Cardiol J};2011;18(3):318-319.
4. Levy D, Ronemus M, Yamrom B, Lee YH, Leotta A, Kendall J, Marks S, Lakshmi B, Pai D, Ye K, Buja A, Krieger A, Yoon S, Troge J, Rodgers L, Iossifov I, Wigler M. {{Rare de novo and transmitted copy-number variation in autistic spectrum disorders}}. {Neuron};2011 (Jun 9);70(5):886-897.
To explore the genetic contribution to autistic spectrum disorders (ASDs), we have studied genomic copy-number variation in a large cohort of families with a single affected child and at least one unaffected sibling. We confirm a major contribution from de novo deletions and duplications but also find evidence of a role for inherited « ultrarare » duplications. Our results show that, relative to males, females have greater resistance to autism from genetic causes, which raises the question of the fate of female carriers. By analysis of the proportion and number of recurrent loci, we set a lower bound for distinct target loci at several hundred. We find many new candidate regions, adding substantially to the list of potential gene targets, and confirm several loci previously observed. The functions of the genes in the regions of de novo variation point to a great diversity of genetic causes but also suggest functional convergence.
5. Nayate A, Tonge BJ, Bradshaw JL, McGinley JL, Iansek R, Rinehart NJ. {{Differentiation of High-Functioning Autism and Asperger’s Disorder Based on Neuromotor Behaviour}}. {J Autism Dev Disord};2011 (Jun 10)
Autism and Asperger’s disorder (AD) are characterised by impairments in social interaction, stereotypic behaviours or restricted interests. Although currently listed as distinct clinical disorders, the validity of their distinction remains controversial. This study examined gait in children with autism and AD. Eleven children with high-functioning autism and eleven children with AD completed a series of walking tasks. Results indicated distinct movement disturbance; these findings are discussed in light of seminal papers in this field by Vilensky et al. (Arch Neurol 38:646-649, 1981) and Hallett et al. (Arch Neurol 50:1304-1308, 1993) who interpret the gait of individuals with autism using parkinsonian and cerebellar-ataxia patient models, respectively. Distinctions in gait patterns implicating perhaps unique motor circuit disturbances support the hypothesis that autism and AD may have unique neurodevelopmental trajectories.
6. Saalasti S, Tiippana K, Katsyri J, Sams M. {{The effect of visual spatial attention on audiovisual speech perception in adults with Asperger syndrome}}. {Exp Brain Res};2011 (Jun 10)
Individuals with Asperger syndrome (AS) have problems in following conversation, especially in the situations where several people are talking. This might result from impairments in audiovisual speech perception, especially from difficulties in focusing attention to speech-relevant visual information and ignoring distracting information. We studied the effect of visual spatial attention on the audiovisual speech perception of adult individuals with AS and matched control participants. Two faces were presented side by side, one uttering /aka/ and the other /ata/, while an auditory stimulus of /apa/ was played. The participants fixated on a central cross and directed their attention to the face that an arrow pointed to, reporting which consonant they heard. We hypothesized that the adults with AS would be more distracted by a competing talking face than the controls. Instead, they were able to covertly attend to the talking face, and they were as distracted by a competing face as the controls. Independently of the attentional effect, there was a qualitative difference in audiovisual speech perception: when the visual articulation was /aka/, the control participants heard /aka/ almost exclusively, while the participants with AS heard frequently /ata/. This finding may relate to difficulties in face-to-face communication in AS.
7. Sanders SJ, Ercan-Sencicek AG, Hus V, Luo R, Murtha MT, Moreno-De-Luca D, Chu SH, Moreau MP, Gupta AR, Thomson SA, Mason CE, Bilguvar K, Celestino-Soper PB, Choi M, Crawford EL, Davis L, Davis Wright NR, Dhodapkar RM, Dicola M, Dilullo NM, Fernandez TV, Fielding-Singh V, Fishman DO, Frahm S, Garagaloyan R, Goh GS, Kammela S, Klei L, Lowe JK, Lund SC, McGrew AD, Meyer KA, Moffat WJ, Murdoch JD, O’Roak BJ, Ober GT, Pottenger RS, Raubeson MJ, Song Y, Wang Q, Yaspan BL, Yu TW, Yurkiewicz IR, Beaudet AL, Cantor RM, Curland M, Grice DE, Gunel M, Lifton RP, Mane SM, Martin DM, Shaw CA, Sheldon M, Tischfield JA, Walsh CA, Morrow EM, Ledbetter DH, Fombonne E, Lord C, Martin CL, Brooks AI, Sutcliffe JS, Cook EH, Jr., Geschwind D, Roeder K, Devlin B, State MW. {{Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism}}. {Neuron};2011 (Jun 9);70(5):863-885.
We have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6-12.0, p = 2.4 x 10(-7)). We estimate there are 130-234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1.
8. Schaaf CP, Zoghbi HY. {{Solving the autism puzzle a few pieces at a time}}. {Neuron};2011 (Jun 9);70(5):806-808.
In this issue, a pair of studies (Levy et al. and Sanders et al.) identify several de novo copy-number variants that together account for 5%-8% of cases of simplex autism spectrum disorders. These studies suggest that several hundreds of loci are likely to contribute to the complex genetic heterogeneity of this group of disorders. An accompanying study in this issue (Gilman et al.), presents network analysis implicating these CNVs in neural processes related to synapse development, axon targeting, and neuron motility.
9. Silva LM, Schalock M, Ayres R. {{A model and treatment for autism at the convergence of Chinese medicine and Western science: First 130 cases}}. {Chin J Integr Med};2011 (Jun);17(6):421-429.
OBJECTIVE: To present a model for autism showing that impairment of sensory and self-regulation is the core deficit that underlies delays in social/language skills and abnormal behavior in autism; and to demonstrate the efficacy of a treatment for autism based on Chinese medicine. METHODS: Children with autism under 6 years of age were assigned to treatment or wait-list conditions. A total of 130 children were treated and the results compared with 45 wait-list controls. Treatment is a tuina methodology directed at sensory impairment-Kai Qiao Tuina. The treatment was a five-month protocol that was implemented daily by trained parents via trained support staff. The effects of treatment on the main symptoms, autistic behavior, social/language delay, sensory and self-regulatory impairment, as well as on parenting stress, were observed and compared. RESULTS: The treatment had a large effect size (P<0.0001) on measures of sensory and self-regulation. The evaluations done by pre-school teachers demonstrated improvement in the measures of autism (P<0.003), and were confirmed by evaluations done by parents (P<0.0001). There was a large decrease (P<0.0001) in parenting stress. CONCLUSIONS: Sensory and self-regulatory impairment is a main factor in the development and severity of autism. Treatment of young children with autism with Kai Qiao Tuina resulted in a decrease in sensory and self-regulatory impairment and a reduction in severity of measures of autism.
10. Sung M, Ooi YP, Goh TJ, Pathy P, Fung DS, Ang RP, Chua A, Lam CM. {{Effects of Cognitive-Behavioral Therapy on Anxiety in Children with Autism Spectrum Disorders: A Randomized Controlled Trial}}. {Child Psychiatry Hum Dev};2011 (Jun 10)
We compared the effects of a 16-week Cognitive-Behavioral Therapy (CBT) program and a Social Recreational (SR) program on anxiety in children with Autism Spectrum Disorders (ASD). Seventy children (9-16 years old) were randomly assigned to either of the programs (n (CBT) = 36; n (SR) = 34). Measures on child’s anxiety using the Spence Child Anxiety Scale-Child (SCAS-C) and the Clinical Global Impression-Severity scale (CGI-S) were administered at pre-, post-treatment, and follow-ups (3- and 6-month). Children in both programs showed significantly lower levels of generalized anxiety and total anxiety symptoms at 6-month follow-up on SCAS-C. Clinician ratings on the CGI-S demonstrated an increase in the percentage of participants rated as « Normal » and « Borderline » for both programs. Findings from the present study suggest factors such as regular sessions in a structured setting, consistent therapists, social exposure and the use of autism-friendly strategies are important components of an effective framework in the management of anxiety in children and adolescents with ASD.
11. Whitman SA, Cover C, Yu L, Nelson DL, Zarnescu DC, Gregorio CC. {{Desmoplakin and Talin2 Are Novel mRNA Targets of Fragile X-Related Protein-1 in Cardiac Muscle Whitman; Dsp and Tln2 Are mRNA Targets of FXR1 in the Heart}}. {Circ Res};2011 (Jun 9)
Rationale: The proper function of cardiac muscle requires the precise assembly and interactions of numerous cytoskeletal and regulatory proteins into specialized structures that orchestrate contraction and force transmission. Evidence suggests that posttranscriptional regulation is critical for muscle function, but the mechanisms involved remain understudied. Objective: To investigate the molecular mechanisms and targets of the muscle-specific fragile X mental retardation, autosomal homolog 1 (FXR1), an RNA binding protein whose loss leads to perinatal lethality in mice and cardiomyopathy in zebrafish. Methods and Results: Using RNA immunoprecipitation approaches we found that desmoplakin and talin2 mRNAs associate with FXR1 in a complex. In vitro assays indicate that FXR1 binds these mRNA targets directly and represses their translation. Fxr1 KO hearts exhibit an up-regulation of desmoplakin and talin2 proteins, which is accompanied by severe disruption of desmosome as well as costamere architecture and composition in the heart, as determined by electron microscopy and deconvolution immunofluorescence analysis. Conclusions: Our findings reveal the first direct mRNA targets of FXR1 in striated muscle and support translational repression as a novel mechanism for regulating heart muscle development and function, in particular the assembly of specialized cytoskeletal structures.
12. Zachor DA, Ben Itzchak E. {{Assisted reproductive technology and risk for autism spectrum disorder}}. {Res Dev Disabil};2011 (Jun 7)
Epidemiologic studies on maternal and pregnancy risk factors for autism spectrum disorder (ASD), including use of assisted reproductive technology (ART), found conflicting results. This study included the following aims: to assess frequencies of ART in a large ASD group; to examine confounding birth and familial risk factors in the ASD with ART group; to examine possible relationships between ART and autism severity, adaptive skills and developmental trajectory. The study included 624 participants, 507 diagnosed with ASD. Autism severity and adaptive skills were assessed using standardized tests. Extensive medical, familial and developmental histories were obtained. The rate of ART in the ASD group was significantly higher (10.7%) than in a large Israeli population (3.06%). Parental age’s distribution did not differ in both ASD groups, with and without ART. Although maternal age was more advanced in the ASD group, the frequency of ART in young mothers (<29 years) was still significantly high (8.7%). The frequencies of gestational age <36 weeks and low birth weight (<2500g) in the ASD with ART singleton group and in the Israeli population were not significantly different. None of the ASD with ART group and 14.7% in the ASD without ART group had a relative with ASD. Autism severity, adaptive skills and developmental regression were not significantly different in the ASD with and without ART groups. This pilot study points to the role of assisted conception as a risk factor for ASD. However, this group of ASD with ART does not represent a separate clinical phenotype in ASD.
