Construction of copy number variation landscape and characterization of associated genes in a Bangladeshi cohort of neurodevelopmental disorders

Introduction: Copy number variations (CNVs) play a critical role in the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics in an ethnically underrepresented homogenous population of Bangladesh. Methods: We have conducted chromosomal microarray analysis (CMA) for 212 NDD patients with male to female ratio of 2.2:1.0 to identify rare CNVs. To identify candidate genes within the rare CNVs, gene constraint metrics [i.e., “Critical-Exon Genes (CEGs)”] were applied to the population data. Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) was followed in a subset of 95 NDD patients to assess the severity of autism and all statistical tests were performed using the R package. Results: Of all the samples assayed, 12.26% (26/212) and 57.08% (121/212) patients carried pathogenic and variant of uncertain significance (VOUS) CNVs, respectively. While 2.83% (6/212) patients’ pathogenic CNVs were found to be located in the subtelomeric regions. Further burden test identified females are significant carriers of pathogenic CNVs compared to males (OR = 4.2; p = 0.0007). We have observed an increased number of Loss of heterozygosity (LOH) within cases with 23.85% (26/109) consanguineous parents. Our analyses on imprinting genes show, 36 LOH variants disrupting 69 unique imprinted genes and classified these variants as VOUS. ADOS-2 subset shows severe social communication deficit (p = 0.014) and overall ASD symptoms severity (p = 0.026) among the patients carrying duplication CNV compared to the CNV negative group. Candidate gene analysis identified 153 unique CEGs in pathogenic CNVs and 31 in VOUS. Of the unique genes, 18 genes were found to be in smaller (<1 MB) focal CNVs in our NDD cohort and we identified PSMC3 gene as a strong candidate gene for Autism Spectrum Disorder (ASD). Moreover, we hypothesized that KMT2B gene duplication might be associated with intellectual disability. Conclusion: Our results show the utility of CMA for precise genetic diagnosis and its integration into the diagnosis, therapy and management of NDD patients

WASH, nutrition and health-seeking behavior during COVID-19 lockdowns: Evidence from rural Bangladesh

A general lockdown to minimize to slow transmission of COVID-19 in Bangladesh came into effect on March 26th and lasted until May 30th. The lockdown had far-reaching economic implications for the population, with many facing economic hardship due to loss of income. Despite the attempt of the government to ease economic hardship by means of social safety net packages, people suffered from poor access to health services, and financial and food insecurity. This is likely to have disastrous consequences for the nutritional status of young children. This cross-sectional study measured the impact of the first general lockdown on food consumption of young children, access to water, handwashing and health seeking behavior, and the ability to maintain livelihood among households with children under the age of 5, in rural Bangladesh. The result of the analysis suggest that loss of income was reported by almost all respondents across all socio-economic groups. However, the poorest households were less likely to provide for sufficient food for their families and had to reduce consumption of food. Diet diversity and food intake–particularly animal protein sources—for young children were severely affected. On the other, increased awareness of handwashing and access to soap were also reported. The pandemic is likely to be detrimental to the nutritional status of children in Bangladesh and can exacerbate existing health inequities. Strong social safety net programs are needed to protect vulnerable populations to consequences of restrictive measures, supported in design and implementation by non-governmental organizations