Bangabandhu Sheikh Mujib Medical University

Primary Ovarian Insufficiency (POI), a significant cause of female infertility, involves premature ovarian dysfunction before the age of 40 and is influenced by genetic predispositions, autoimmune disorders, environmental factors, and metabolic changes. In this study, we employed Whole Exome Sequencing (WES) to explore genetic variations linked to POI in Bangladeshi women.

This study encompassed 30 Bangladeshi women aged 16 to 40 diagnosed with POI. The diagnosis was based on clinical criteria, including elevated Follicle-Stimulating Hormone levels and a history of at least four months of oligomenorrhea or amenorrhea. WES was performed on POI cases and used population specific internal cohort to filter out and identify genes impacting ovarian function. Subsequently, Sanger Sequencing was used to validate pathogenic or likely pathogenic variants.

We detected seven pathogenic variants in 23% of all POI cases (7/30) across six genes: Thyroglobulin (TG), Thyroid-Stimulating Hormone Receptor (TSHR), tubulin beta 8 class viii (TUBB8), PR/SET domain 9 (PRDM9), required for meiotic nuclear division 1 homolog (RMND1), and homologous recombination factor with OB-fold (HROB). Two novel likely pathogenic variants were identified, including a heterozygous frameshift variant in TG (p.H209Pfs11) and a heterozygous missense variant in TSHR (p.T1904C). Additionally, variants of uncertain significance were found in 63% (19/30) of the cases, with seven being novel. Incidental findings of pathogenic variants were observed in several genes, with Hemoglobin subunit Beta (HBB) being the most common.

This study highlights the utility of whole exome sequencing in identifying genetic risk factors for POI, suggesting that incorporating genetic screening into routine clinical practice could improve diagnostic and therapeutic strategies, particularly in regions lacking genomic data on this condition.

Background: Although national population-based birth defect prevalence estimates are unavailable for Bangladesh specifically, data extrapolated from the March Dimes Global Birth Defects Report indicate a prevalence of neural tube defects (NTDs) of 4.7 per 1,000 live births.Purpose: This study aimed to determine the prevalence of NTD among infants born at a tertiary care multidisciplinary referral hospital in Bangladesh.Methods: Live born infants with NTD were prospectively enrolled in 2015–2021. Each enrolled NTD case was examined for type, location, and associated anomalies. The overall and annual prevalence rates were then calculated.Results: A total of 10,372 newborns were enrolled; of them, 68 had NTD (incidence, 6.4 [range, 4.59–11.2] per 1,000 live births). The mean maternal age was 27.49± 4.72 years. Three-quarters of the NTD cases were detected at birth, and 94% of the mothers reported not taking periconceptional folic acid supplements. The meningomyelocele complex was the most frequent location. Two peaks in incidence were noted in 2017 and 2021 (10.28 and 11.2 per 1,000 live births, respectively). The distribution of different NTD types included meningomyelocele at 53%, encephalocele at 26.6%, meningocele at 16%, and anencephaly at 4.4%. A male predominance was noted overall except for anencephaly. The most common location was the lumbosacrum (47%). The NTD was isolated in 20.59% (14 of 68) of cases and associated with other malformations in 80% (54 of 68) of cases.Conclusion: The incidence of NTD was 6.4 per 1,000 live births at a leading tertiary care multidisciplinary referral center in Bangladesh. However, this figure might not reflect the incidence of NTD in the wider population.