SHANK3 genetic polymorphism and susceptibility to ASD: evidence from molecular, in silico, and meta-analysis approaches.

BACKGROUND: The SHANK3 gene encodes a master synaptic scaffolding protein at the excitatory synapse's postsynaptic density, which is predominantly responsible for constructing a synapse, maintaining synaptic structure, and functions. Recently, evidence from rare mutations and copy number variation provided an important clue about SHANK3 which acts as a strong candidate gene in the pathogenesis of Autism Spectrum Disorder (ASD). MATERIALS AND METHODS: To investigate potential allelic variants for the SHANK3 (rs9616915) gene as a genetic risk factor, we performed PCR-RFLP analysis and Sanger sequencing for 90 ASD and 90 healthy subjects. Moreover, to understand the functional and structural impacts of our selected non-synonymous SHANK3 SNP rs9616915, we have performed an in silico analysis. Subsequently, a meta-analysis of rs9616915 with a total of 6 eligible studies (including the present study) containing a total of 795 cases and 12,947 controls was obtained from a comprehensive online database search to evaluate the overall association with ASD. RESULTS: Our retrieved data, such as Pearson's chi-square test (p = 0.081) as well as logistic regression analysis of co-dominant (p = 0.1131), dominant (p = 0.3656) and recessive models (p = 0.0569) speculated no significant association between rs9616915 and our studied sample. Interestingly, by in silico analysis, we have observed two hydrogen bonds between amino acids instead of one hydrogen bond in the protein structure of rs9616915, which indicates this mutant structure could affect the proteins' stability. The findings of the meta-analysis revealed that four genetic association models were associated with ASD susceptibility. CONCLUSIONS: Our study suggested that targeted SHANK3 SNP of interest rs9616915 might not be associated with ASD in the southern part of the Bangladeshi population.

Prevalence of epilepsy in Bangladesh: Results from a national household survey.

OBJECTIVE: To determine the prevalence and types of epilepsy in Bangladesh. METHODS: We conducted a nationwide population-based cross-sectional survey among Bangladeshi population of all ages, except children under one month. We surveyed 9839 participants (urban, 4918; rural, 4920) recruited at their households using multistage cluster sampling. Trained physicians with neurology background confirmed the diagnosis of suspected epilepsy cases identified by interviewer-administered questionnaires. We reported the overall and sex, residence, and age groups-specific prevalence of epilepsy per 1000 populations with 95% confidence interval. RESULTS: The national prevalence of epilepsy per 1000 was 8.4 (95% CI 5.6-11.1), urban 8.0 (4.6-11.4), and rural 8.5 (5.60-11.5). The prevalence in adult males and females was 9.2 (5.7-12.6) and 7.7 (3.6-11.7), respectively. The prevalence in children aged <18 years (8.2, 3.4-13.0 was similar to adults (8.5 (5.4-11.4). Among all epilepsy cases, 65.1% had active epilepsy. Their (active epilepsy) prevalence was 5.8 (3.5-8.1). Of them, 63.4% were not receiving treatment. Moreover, those who received allopathy treatment, 72.5% had low adherence leading to a high treatment gap. SIGNIFICANCE: Our findings out of this first-ever national survey were similar to other Asian countries. However, the prevalence of active epilepsy and treatment gap were considerably higher. This study serves useful evidence for tailoring interventions aimed to reduce the burden of epilepsy-primarily through targeted community awareness program-and access to antiepileptic treatment in health facilities in Bangladesh.

Mutation Spectrum of ß-Thalassemia and Other Hemoglobinopathies in Chittagong, Southeast Bangladesh.

Thalassemia is one of the most common autosomal recessive blood disorders in the world. It shows a variety of clinical expression, starting from asymptomatic to severe blood transfusion dependence. More than 500 alleles have been characterized in or around the ß-globin region. Moreover, most geographical regions have their own characteristics, frequency and availability of these alleles, predominantly circulating within the communities present in that particular region. In this study, we explored the spectrum of ß-thalassemia (ß-thal) alleles present in Chittagong, Southeast Bangladesh. This study comprises ß-thal and Hb E (HBB: c.79 G > A) patients from in and around the area of Chittagong. Not only exploring the complete ß-globin mutation spectrum of the area, but we also tried to look at the origin of the mutated alleles. The ß-thal mutations of Bangladesh show a relatively wide spectrum of alleles, which further demonstrates the heterogeneity of the disease in this country. Although our study showed that the majority of the mutations have their origin in neighboring countries such as India, countries of Southeast Asia, Pakistan, etc., some unusual alleles do not originate in neighboring countries and put a little more diversity in the overall spectrum of ß-thal-specific alleles. Overall, this study demonstrates the mutation spectrum related to ß-thal in Chittagong, Southeast Bangladesh.