G9055a Substitution in Mtdna: An Important Variant in Autism
Autism spectrum disorders [ASDs] are neurodevelopmental complex diseases with causative de-novo and inherited genetic factors. They contain a range of cognitive and behavioral conditions such as Asperger's syndrome, pervasive developmental disorder and autism. Our study cases were children with autistic behaviors [15-60 CARS Score]. The DNA extraction process was done by GeNet Bio DNA extraction kit, and the region of interest was amplified using independent PCR runs. After purification of PCR products, both strands were sequenced by a Big Dye Termination system. The automated sequencing on an ABI 3700 was directly determined with a capillary sequencer machine. Both primers sequencing results were analysed using bioinformatics' tool, Sequencher Software 5. In this study, 31 samples were examined which 14 unique variants were detected in genes related to ATPase6/8 and tRNA. One of the variants known as G9055A [CAAD>20 and PolyPhen is shown to be Probably damaging] seems pathogenic according to PolyPhen and CADD scores. In the variant G9055A of ATP6, amino acid alanine converts to threonine. A to T substitutions induce accumulation of amiloid fibril in the brain because threonine prefers to form βsheet as a necessary stage in the amyloidogenic process. In our study of patients with autism, we found one case having an interesting association with amyloidosis. It is hoped that by finding such markers, the children will be treated with more certainty.
Index Terms - Amyloidogenic process, Autism spectrum disorders, mtDNA variation.