Many studies have supported a genetic etiology for autism. Here we report mutations in two X-linked genes encoding neuroligins NLGN3 and NLGN4 in siblings with autism-spectrum disorders. These mutations affect cell-adhesion molecules localized at the synapse and suggest that a defect of synaptogenesis may predispose to autism.

Over the last 20 years, melatonin, a pineal hormone synthesized from serotonin, has been implicated in various studies on the autism spectrum disorder (ASD) and altered melatonin levels were detected in subgroups of subjects with ASD. Its effect on sleep disturbances got the attention of clinicians and several investigations were carried out to determine the usefulness and safety of melatonin administration in this disorder. Hypotheses were also raised regarding the possibility that the dysfunctional synthesis and secretion of melatonin detected in subgroups of subjects with ASD may increase the risk as well the severity of ASD. The purpose of this paper is to review our pharmacokinetic knowledge on melatonin and present results from recent studies on sleep disorders in autism, their treatment with melatonin and the impact of melatonin prescription in children with ASD evaluated in a Diagnostic Center for Autism Spectrum Disorder in Paris, France.

Infantile autism is a pervasive developmental disorder with a strong genetic component. The mode of inheritance appears to be complex and no specific susceptibility genes have yet been identified. Chromosome 16p13.3 may contain a susceptibility gene based on findings from genome scans and reports of chromosome abnormalities in individuals with autism. The somatostatin receptor 5 (SSTR5) gene is located on chromosome 16p13.3 and is thus a positional candidate gene for autism. SSTR5 may also be a functional candidate gene for autism because somatostatin inhibits growth hormone secretion, and increased growth hormone response has been reported in some individuals with autism. Moreover, the somatostatinergic system interacts with the dopaminergic system, which has been hypothesized to be involved in the etiology of autism; in particular, somatostatin secretion is regulated by dopamine, and the dopamine D2 receptor and the SSTR5 receptor interact to form a receptor complex with enhanced functional activity. In the present study, we tested whether the alleles of twelve new single nucleotide polymorphisms (SNPs) in the SSTR5 gene were preferentially transmitted, using the transmission disequilibrium test (TDT) in a sample of 79 trios with autism (18 from Denmark and 61 from France). Furthermore, we combined four missense SNPs into haplotypes and searched for preferential transmission using the program TRANSMIT. No significant preferential transmission of the alleles and haplotypes of the twelve SNPs was found. Our results do not suggest the SSTR5 gene as a susceptibility gene for autism.

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