New Study Identifies Several Inherited Mutations in Autism

New Study Identifies Several Inherited Mutations in Autism

Until recently, although researchers observed that autism is somehow related to genetic transmission, only a handful of causes have been found. One of the main reasons why not enough data exists is because of the high variety of mutations that are behind the disease. However, a team of researchers from the Children’s Hospital in Boston managed to pinpoint some mutations through the use of whole-exome sequencing. Theirs studies were done on large Middle Eastern families that suffer from autism. Their study was just published in the journal Neuron.

Autism

According to the research team, they found that multiple genes that are implicated in different genetic syndromes may also suffer a less sever mutation and become the cause of autism. Tim Yu, Maria Chahrour and Christopher Walsh, the three leaders of the research team, began their study with three large families from the Middle East. Each family had at least two children who suffered from ASDs (Autism Spectrum Disorders). They searched each family for traces of recessive mutations. According to Dr Walsh, they investigated Middle Eastern families due to the fact that US families are usually smaller.The parents from all the three families that were investigated are first cousins. This is a common tradition in Middle Eastern families, and has aided the research greatly. Genetic mapping techniques were used to narrow the search to various specific chromosomal locations. This was followed by the sequencing of protein-coding genes (also known as whole-exome sequencing). The investigators discovered three new mutated genes that weren’t formerly associated with autism. However, one of these genes, the AMT gene, is associated with glycine encephalopathy, a very sever metabolic syndrome with exclusively neurological symptoms. The second gene, known as PEX7, is related to rhizomelic chondrodysplasia punctata, a genetic syndrome that causes seizures, congenital cataracts and death. The third gene, named SYNE1 is associated with severe motor problems and brain malformations. All these syndromes include either intellectual disabilities or autistic behavior, but neither are considered to be the primary symptom.

Maria Chahrour, the first author of the study, notes that their research is the first to link these three genes to autism. She added that “The AMT and PEX7 mutations weren’t picked up by standard tests for metabolic disorders, but when you’re able to sequence the entire exome, you can find them”. A total of 163 Middle Eastern families which had two or more children suffering from autism were included in the study. The scientists searched for different metabolic and genetic syndromes that affect the brain functions. A total of 70 genes were studied, all implicated in different syndromes. They used the same whole-exome sequencing technique in order to analyze the mutations of these genes, thus allowing them to discover several new mutations that can be linked to autism spectrum disorders. Researchers also linked the genes VPS13B, POMGNT1 and MECP2. The first gene is linked to the Cohen syndrome, the second gene is linked to several brain malformations, whilst the third gene is linked to Rett syndrome.

“We have textbook descriptions of all these diseases, but in real life, there can be atypical, milder presentations of the same disease,” says Yu, also a first author in the study. Along with the Middle Eastern families, researchers also investigated data from 612 families from the United States and found at least two gene mutations that were similar in both family cohorts. According to Yu, further studies will allow a rough estimation on the number of autism cases that follow this pattern.