1. Buizer-Voskamp JE, Franke L, Staal WG, van Daalen E, Kemner C, Ophoff RA, Vorstman JA, van Engeland H, Wijmenga C. {{Systematic genotype-phenotype analysis of autism susceptibility loci implicates additional symptoms to co-occur with autism}}. {Eur J Hum Genet};2009 (Nov 25)
Many genetic studies in autism have been performed, resulting in the identification of multiple linkage regions and cytogenetic aberrations, but little unequivocal evidence for the involvement of specific genes exists. By identifying novel symptoms in these patients, enhanced phenotyping of autistic individuals not only improves understanding and diagnosis but also helps to define biologically more homogeneous groups of patients, improving the potential to detect causative genes. Supported by recent copy number variation findings in autism, we hypothesized that for some susceptibility loci, autism resembles a contiguous gene syndrome, caused by aberrations within multiple (contiguous) genes, which jointly increases autism susceptibility. This would result in various different clinical manifestations that might be rather atypical, but that also co-occur with autism. To test this hypothesis, 13 susceptibility loci, identified through genetic linkage and cytogenetic analyses, were systematically analyzed. The Online Mendelian Inheritance in Man database was used to identify syndromes caused by mutations in the genes residing in each of these loci. Subsequent analysis of the symptoms expressed within these disorders allowed us to identify 33 symptoms (significantly more than expected, P=0.037) that were over-represented in previous reports mapping to these loci. Some of these symptoms, including seizures and craniofacial abnormalities, support our hypothesis as they are already known to co-occur with autism. These symptoms, together with ones that have not previously been described to co-occur with autism, might be considered for use as inclusion or exclusion criteria toward defining etiologically more homogeneous groups for molecular genetic studies of autismEuropean Journal of Human Genetics advance online publication, 25 November 2009; doi:10.1038/ejhg.2009.206.
2. Coskun MA, Varghese L, Reddoch S, Castillo EM, Pearson DA, Loveland KA, Papanicolaou AC, Sheth BR. {{Increased response variability in autistic brains?}} {Neuroreport};2009 (Nov 25);20(17):1543-1548.
One of the key ideas regarding atypical connectivity in autistic brains is the hypothesis of noisier networks. The systems level version of this hypothesis predicts reduced reliability or increased variability in the evoked responses of individuals with autism. Using magnetoencephalography, we examined the response of individuals with autism spectrum disorder versus matched typically developing persons to passive tactile stimulation of the thumb and index finger of the dominant (right) hand. A number of different analyses failed to show higher variability in the evoked response to the thumb or to the index finger in the autism group as compared with typicals. Our results argue against the hypothesis that the brain networks in autism are noisier than normal.
