Duchenne muscular dystrophy (DMD) is a severe rare neuromuscular disorder caused by mutations in the X-linked dystrophin gene. Several mutations have been identified, yet the full mutational spectrum, and their phenotypic consequences, will require genotyping across different populations. To this end, we undertook the first detailed genotype and phenotype characterization of DMD in the Bangladeshi population. We investigated the rare mutational and phenotypic spectrum of the DMD gene in 36 DMD-suspected Bangladeshi participants using an economically affordable diagnostic strategy involving initial screening for exonic deletions in the DMD gene via multiplex PCR, followed by testing PCR-negative patients for mutations using whole exome sequencing. The deletion mapping identified two critical DMD gene hotspot regions (near proximal and distal ends, spanning exons 8-17 and exons 45-53, respectively) that comprised 95% (21/22) of the deletions for this population cohort. From our exome analysis, we detected two novel pathogenic hemizygous mutations in exons 21 and 42 of the DMD gene, and novel pathogenic recessive and loss of function variants in four additional genes: SGCD, DYSF, COL6A3, and DOK7. Our phenotypic analysis showed that DMD suspected participants presented diverse phenotypes according to the location of the mutation and which gene was impacted. Our study provides ethnicity specific new insights into both clinical and genetic aspects of DMD.

The study was conducted to assess the prevalence of microalbuminuria in non-diabetic hypertensive individuals with or without antihypertensive medication(s), attending medicine outpatient department of Dhaka Medical College Hospital. Non-diabetic hypertensive individuals without a history of pre-existing kidney diseases participated in this cross-sectional study. A questionnaire was used for collecting information on demographics, life style and family history of cardiovascular and kidney disease. Spot morning urine samples were collected for albumin estimation. Albuminuria thresholds were evaluated and defined using albumin-creatinine ratio (ACR). A total of 500 non-diabetic hypertensive individuals (310 males, 190 females) aged 52.25+/-7.99 years were enrolled in this study. After excluding 08 persons with macroalbuminuria, microalbuminuria was found in 51 cases (10.37%) [7.68%-13.06%].The prevalence was higher in females than males, ie 11.89% [7.23%- 16.55%] and 9.45% [6.18%-12.72%] respectively. There was no statistical significant difference between the sex groups. Duration of blood pressure showed statistical significant association with the occurrence of microalbuminuria. This suggests that, in Bangladeshi hypertensive individuals microalbuminuria is not uncommon. Further prospective studies with large sample size in different areas of the country are needed to confirm the prevalence of microalbuminuria in such individuals. The causative factors as well as prognostic value of the occurrence of microalbuminuria in this population remain to be determined in prospective cohort studies.

This study explored the physical and clinical phenotype of Bangladeshi children with autism spectrum disorder (ASD). A totally of 283 children who were referred for screening and administered Module 1 of the Autism Diagnostic Observation Schedule (ADOS) were included. Overall, 209 met the ADOS algorithmic cutoff for ASD. A trend for greater weight and head circumference was observed in children with ASD versus non-ASD. Head circumference was significantly (p < 0.03) larger in ASD males compared with non-ASD males. A trend was also observed for symptom severity, higher in females than males (p = 0.068), with further analyses demonstrating that social reciprocity (p < 0.014) and functional play (p < 0.03) were significantly more impaired in ASD females than males. The findings help understand sex differences in ASD.

Abstract Background Intellectual disability (ID) is a complex condition that can impact multiple domains of development. The genetic contribution to ID’s etiology is significant, with more than 100 implicated genes and loci currently identified. The majority of such variants are rare and de novo genetic mutations. Methods We have applied whole‐genome microarray to identify large, rare, clinically relevant copy number variants (CNVs). We have applied well‐established algorithms for variants call. Quantitative polymerase chain reaction (qPCR) was applied to validate the variants using three technical replicates for each family member. To assess whether the copy number variation was due to balanced translocation or mosaicism, we further conducted droplet digital PCR (ddPCR) on the whole family. We have, as well, applied “critical‐exon” mapping, human developmental brain transcriptome, and a database of known associated neurodevelopmental disorder variants to identify candidate genes. Results Here we present two siblings who are both impacted by a large terminal duplication and a deletion. Whole‐genome microarray revealed an 18.82 megabase (MB) duplication at terminal locus (7q34‐q36.3) of chromosome 7 and a 3.90 MB deletion impacting the terminal locus (15q26.3) of chromosome 15. qPCR and ddPCR experiments confirmed the de novo origin of the variants and the co‐occurrence of these two de novo events among the siblings, but their absence in both parents, implicates an unbalanced translocation that could have mal‐segregated among the siblings or a possible germline mosaicism. These terminal events impact IGF1R, CNTNAP2, and DPP6, shown to be strongly associated with neurodevelopmental disorders. Detailed clinical examination of the siblings revealed the presence of both shared and distinct phenotypic features. Conclusions This study identified two large rare terminal de novo events impacting two siblings. Further phenotypic investigation highlights that even in the presence of identical large high penetrant variants, spectrum of clinical features can be different between the siblings.

Background Genetic testing is becoming an essential tool for breast cancer (BC) diagnosis and treatment pathway, and particularly important for early detection and cancer prevention. The purpose of this study was to explore the diagnostic yield of targeted sequencing of the high priority BC genes. Methods We have utilized a cost-effective targeted sequencing approach of high priority actionable BC genes (BRCA1, BRCA2, ERBB2 and TP53) in a homogeneous patient cohort from Bangladesh (n = 52) by using tumor and blood samples. Results Blood derived targeted sequencing revealed 25.58% (11/43) clinically relevant mutations (both pathogenic and variants of uncertain significance (VUS)), with 13.95% (6/43) of samples carrying a pathogenic mutations. We have identified and validated five novel pathogenic germline mutations in this cohort, comprising of two frameshift deletions in BRCA2, and missense mutations in BRCA1, BRCA2 and ERBB2 gene respectively. Furthermore, we have identified three pathogenic mutations and a VUS within three tumor samples, including a sample carrying pathogenic mutations impacting both TP53 (c.322dupG; a novel frameshift insertion) and BRCA1 genes (c.116G > A). 22% of tissue samples had a clinically relevant TP53 mutation. Although the cohort is small, we have found pathogenic mutations to be enriched in BRCA2 (9.30%, 4/43) compare to BRCA1 (4.65%, 2/43). The frequency of germline VUS mutations found to be similar in both BRCA1 (4.65%; 2/43) and BRCA2 (4.65%; 2/43) compared to ERBB2 (2.32%; 1/43). Conclusions This is the first genetic study of BC predisposition genes in this population, implies that genetic screening through targeted sequencing can detect clinically significant and actionable BC-relevant mutations.

Introduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder. Due to long term impairment, high genetic component (heritability> 90%), lack of effective prevention and treatment, ASD has been prioritized for genetic studies. Studies on Copy Number Variations (CNV) at chromosome 16p11.2 locus have mostly been conducted in population of pure or predominant European ancestry. It is not known whether this is also prevalent among the ASD affected individuals in population of other ancestries such as Bangladeshi population. The aim of this research work is to detect CNV of SEZ6L2 gene at 16p11.2 locus and to describe the associated clinical characteristics in Bangladeshi cohort with clinically diagnosed ASD. Methods: The known SEZ6L2 gene was interrogated for copy number variation (CNV) in twenty five autistic patients with SYBR Green I assay using the real time qPCR. Probands were interrogated using relative standard curve (efficiency correction) method. Epilepsy with speech disorder and postnatal infection might be more common among autistic patients with CNV at this SEZ6L2 gene. Results: The two cases with characteristics CNV was detected who had clinically manifestation of convulsion at different ages, partial developmental delay in multiple domains including delay in walking, speech delay and mental age not corresponding with the chronological age. This work describes the frequency of CNV is 8.3 %. This rate is skewed due to small sample size and do not reflect the true frequency of 16p11.2 duplication impacting SEZ6L2 gene. Conclusion: Epilepsy with speech disorder and postnatal infection might be more common among autistic patients with CNV at this SEZ6L2 gene. Bangladesh J Medicine Jan 2019; 30(1) : 24-29

Epidermodysplasia verruciformis (EV) is an extremely rare hereditary skin disease characterized by an abnormal susceptibility to the human papilloma virus (HPV) with an increased risk of cutaneous malignancy. Here we report the first female severe EV case in Bangladesh, a 10-year-old girl with a nonsense somatic mutation impacting ANKRD26 gene.