"There are many different genetic mutations causing autism, and they are all very rare. This heterogeneity makes it difficult to develop effective treatments. Our analysis not only revealed a new autism-linked gene, but also identified the mechanism by which its mutation causes autism. Excitingly, mutations in other genes share the same autism-causing mechanism, indicating that we may have underscored a subgroup of ASDs,” explained lead researcher Gaia Novarino, a Professor at IST Austria.
"The identification of novel genes, especially in heterogeneous diseases such as autism, is difficult. However, as result of a collaborative effort, we were able to identify mutations in a gene called SLC7A5 in several patients born to consanguineous marriages and diagnosed with syndromic autism,” commented study co-author Dr. Caglayan, Chairman of the Department of Medical Genetics at the School of Medicine of Istanbul Bilim University in Turkey. The graphical abstract explaining the work is shown in the following figure.
The SLC7A5 gene codes for a transporter protein which likely moves branched-chain amino acids (BCAAs) across the blood brain barrier, into the brain. The researchers utilized mice that lacked the SLC7A5 transporter, causing a reduction of BCAAs in the brain and subsequent impairment in the synthesis of protein production in brain cells. Those mice displayed behavioral changes such as less social interaction that are seen in animal models of autism.
Novarino and colleagues have previously found another gene mutation seen in patients with ASDs, epilepsy and intellectual disability. That gene functions to break down branched chain amino acids. "Of course, not all genes causing autism affect amino acid levels, and these forms of autism are unarguably very rare, but it is possible that even more autism-causing genes fall in this group," explained Novarino.
Intriguingly, the investigators found that some of the neurological dysfunction in the SLC7A5-deficient mice could be treated. After treating the brain with BCAAs directly for three weeks, there was an improvement in the behavioral problems seen in the mice. While such a therapy is not feasible for use in humans, it suggests that ASDs may not be untreatable.
"Our research found a potential treatment for certain symptoms presented in this form of ASD in mice but translation into a treatment for ASD patients will require many years of additional research," said first author Dora Tarlungeanu, a doctoral student in Gaia Novarino's group.
Sources: AAAS/Eurekalert! via Institute of Science and Technology Austria, Cell