Homo sapiens

Autism is the psychiatric pathology with the largest genetic component; 10 to 100 genes are thought to be implicated.

Autistic disorder (MIM#209850) is a multi-factorial and complex neurodevelopmental disorder characterized by three classes of symptoms including:

• impairments in verbal and non-verbal communication,
• impairments in reciprocal social interactions,
• and repetitive or stereotyped behaviors and interests.

Diagnostic assessment is performed before 3 years of age. Symptoms and behaviors are persistent throughout life with changes over the course of development. Autism is a common disorder with the estimate close to 1 per 1,000, more prevalent in boys (sex ratio of 4 male to one female). The genetic etiology of autism was recognized two decades after the first description of autistic children by Pr L Kanner in 1943. The heritability is now estimated at above 90 %. Autism appears to be the most highly genetic of the psychiatric disorders.

Three independent genome-wide scan studies have found some evidence for linkage on chromosome 2q24-q33 region. Screening of genetic variants in nine candidate genes was performed in autistic patients. Two single nucleotide polymorphisms (SNPs), rs2056202 and rs2292813, both within AGC1 gene, showed evidence for divergent distribution between subjects and controls. The two SNPs were further genotyped in 438 autistic families. Evidence for linkage was supported by multipoint non-parametric Lod scores analysis. Excess transmission was found by the transmission disequilibrium test (TDT). AGC1 encodes the calcium-dependent mitochondrial aspartate/glutamate carrier. AGC1 protein is the only form of the mitochondrial aspartate/glutamate carrier expressed in neurons and neural stem cells.
In order to confirm this association and to decipher any potential etiological role of AGC1 in autism, in collaboration with the Centre National de Séquençage at the Genoscope in Evry, we are currently screening for mutations or specific variants in the AGC1 gene in autistic patients.

Since sequencing is the most reliable and efficient method for the detection of polymorphisms and thus a mutation, Genoscope is undertaking the sequencing of PCR products which cover the 18 exons of the ACG1/SLC25A12 gene from 100 patients with autism, a sequencing volume of about 5,000 reads.

Contacts:
Gabor Giapay (Genoscope) - Michel Simonneau (Infobiogen)