Autism and Asperger syndrome fall within a group of disorders classified as pervasive developmental disorders, or PDD. Some argue that Autism and Asperger represent two severities along a single disease continuum. The prevalence of these diseases is estimated to be around 40 per 10,000 for autism and 67 per 10,000 for all PDD’s, according to a report by the CDC in 2000. The principle characteristics of these diseases are impairments in social interaction, stereotypic/repetitive behaviors, and impairments in communication (not so for Asperger’s). About 2/3’s of patients with Autism are mentally retarded. About 25% of children with Autism will also have other dysmorphic features such as microcephaly and structural brain abnormalities. No single gene has surfaced to explain the majority of these conditions despite heritability estimates of more than 90%, suggesting multifactorial inheritance. Work done by Jamain et al., along with supportive findings in our lab, establish a role for neuroligin in the pathogenesis of Autism and Asperger’s.
The neuroligin gene family (NLGN1, 2, 3, 4, and 4Y) codes for cell adhesion molecules situated in the post-synaptic membranes. They interact with neurexins for the maintenance of normal synaptic functions. A triad of studies initially reported the association between neuroligin and autism, Asperger syndrome, and mental retardation. Jamain et al. reported a NLGN3 missense mutation in a pair of Swedish brothers, one with autism, and the other with Asperger syndrome. They also reported a NLGN4 frameshift mutation in another pair of affected brothers, one with autism and the other with Asperger syndrome1. Laumonnier et al. reported a NLGN4 frameshift mutation in a French family in which all affected family members had autism or non-autistic mental retardation2. They also demonstrated co-segregation with disease in six affected and three unaffected individuals within the family. Additionally, they presented the mother of an affected individual, a 34-year-old obligate carrier, who had evidence of mental retardation. Yan et al. reported four NLGN4 missense changes in U.S. Midwest and Portuguese Caucasian families with autism at a frequency of 3% in each population, and no structural changes were found in controls (P=0.009)3. To open a printable assay summary in a new window, click the link below.