Autism spectrum disorders (ASD) are neurodegenerative disorders that are mainly diagnosed based on the behaviors of children, whose symptoms include deficit to develop normal social interaction with other people, impaired development of communicative ability, lack of imaginative ability, and repetitive, stereotyped movements (Casanova et al. 2002). Some changes occur in the anatomy and physiology of brain, such as overgrowth of the frontal cortex during the prenatal period in ASD (Casanova et al. 2002; Talkowski et al. 2012). On the other side, underdeveloped parts in cognitive areas affect decision making, communication and language (Talkowski et al. 2012). Abnormal growth of the hippocampus can affect the development of language syntax, semantics, and the capacity of creativity in language generation and a better understanding of words of a child. One in forty-two boys and one in 189 girls children have ASD worldwide (Autism Speaks, 2018) and the prevalence has increased 10 folds in the last 40 years (Hansen et al. 2015). A new statistic of 2017 shows that the prevalence of ASD among children in the selected countries was found 168, 161, 152, 100, 100, 69, 67, 49, 27, 9.2 per 10000 for USA, Japan, Canada, UK, Ireland, Denmark, Australia, China, Brazil, Portugal, respectively (Hansen et al. 2015). In 2013, a pilot study in Bangladesh found a prevalence of ASD was 0.15% (3% in Dhaka city and 0.07% in the rural area), and the ratio of boys and girls was 4:1 (Global autism movement and Bangladesh, 2014). It is still a case today that diagnosis of ASD lacks unifying theory (Mullegama et al. 2015). Early theories mainly focused on substandard parenting (Mullegama et al., 2015). Newschaffer et al. (2007) suggested that causes of ASD mainly fall into three categories, genetic, environmental and neurobiological. Some other factors like toxicity, teratogenic effect, trauma, infections can also cause ASD (Newschaffer et al. 2007).
Transferrin (TF) (chromosomal location: 3q22.1) is one of the genes which has the most substantial evidence of ASD susceptibility with several independent studies (Davis et al. 2003; Konstantynowicz et al. 2012). TF is an iron transporting plasma glycoprotein that controls the iron level in the biological fluid (Davis et al. 2003). It has two iron binding sites, and these irons accumulate rapidly at the onset of myelination. A very recent study suggested that an elevated extent of oxalate in plasma might play a role in ASD by binding to the bilobal iron transport protein transferrin (hTF) and thereby interfering with iron metabolism by inhibiting iron delivery to cells (Konstantynowicz et al. 2012) So, genetic modification in the transferrin gene may manifest during the generation of ASD (Luck et al. 2013). An investigation was carried out on rs1867503 of transferrin gene and reported that genetic polymorphism of transferrin gene plays a significant role in generating cognitive disorders like ASD (Chaste et al. 2015).
Another particular gene related to ASD is Transcription Factor 4, 18q21.2, (TCF4; also known as E2-2, SEF2 or ITF2) is a basic helix-loop-helix (bHLH) transcription factor (TCF) that is frequently associated with cognitive dysfunction (Sweatt, 2013; Forrest et al. 2014; Hill et al. 2014). Autosomal dominant mutation or deletion of TCF4 results in Pitt Hopkins syndrome (PTHS) and 18q deletion syndrome, three rare ASD (Autistic disorder, Asperger syndrome, and Pervasive developmental disorder) (Brockschmidt et al. 2007; Amiel et al. 2007; Zweier et al. 2007). We found from a previous study TCF4 target genes cluster in neurodevelopmental pathways mostly to schizophrenia, ASD, and ID risk genes (Forrest et al. 2018). These studies proved the association of these genes with ASD in some ethnic groups.
However, there is no study carried out in the Bangladeshi children with ASD to validate the association of rs9951150 variant of the TCF4 gene and rs1867503 of the TF gene. Considering the current situation of ASD in Bangladeshi children, this study was performed with a polymerase chain reaction (PCR) based amplification followed by restriction fragment length polymorphism (RFLP) method to detect TF (rs1867503) and TCF4 (rs9951150) association with ASD, and we hope it will help to understand ASD and to improve their diagnosis and treatment procedure.