A large French family including members affected by nonspecific X-linked mental retardation, with or without autism or pervasive developmental disorder in affected male patients, has been found to have a 2-base-pair deletion in the Neuroligin 4 gene (NLGN4) located at Xp22.33. This mutation leads to a premature stop codon in the middle of the sequence of the normal protein and is thought to suppress the transmembrane domain and sequences important for the dimerization of neuroligins that are required for proper cell-cell interaction through binding to beta-neurexins. As the neuroligins are mostly enriched at excitatory synapses, these results suggest that a defect in synaptogenesis may lead to deficits in cognitive development and communication processes. The fact that the deletion was present in both autistic and nonautistic mentally retarded males suggests that the NLGN4 gene is not only involved in autism, as previously described, but also in mental retardation, indicating that some types of autistic disorder and mental retardation may have common genetic origins.

Weakly to moderately recurrent CNVs (transmitted or occurring de novo) seem to be causative or contributory factors for these diseases. Most of these CNVs (which contain genes involved in neurotransmission or in synapse formation and maintenance) are present in the 3 pathologic conditions (schizophrenia, autism, and mental retardation), supporting the existence of shared biologic pathways in these neurodevelopmental disorders.

Quantified electroencephalography (qEEG) was used to compare cerebral electrical variations while human subjects (10 males and 10 females) were observing and executing finger movements and while they were resting. Video recording enabled elimination of subjects performing involuntary movements. EEGs were recorded from 14 sites in seven frequency bands: theta 1, theta 2, alpha 1, alpha, beta 1, beta 2 and beta 3. Analyses were performed on logarithmically transformed absolute spectral power values. Both observation and execution of finger movements involved a decrease in spectral power compared with resting. This decrease was significant only for the alpha 1 frequency band (7.5-10.5 Hz) and it involved nine of the 14 electrode locations (F7, F8, F4, T6, T5, C3, C4, P3 and P4). This indicates that the motor cortex and the frontal cortex are specifically activated by both observation and execution of finger movements. These results provide evidence that observation and execution of movement share the same cortical network.