http://hdl.handle.net/123456789/17783 Bahria University Health Sciences Campus Islamabad 2026-05-15T18:14:58Z http://hdl.handle.net/123456789/20893 Assessiing Endobronchiiall Washiing Mycobactteriium Tubercullosiis Gene Xpertt''s Rolle iin Diiagnosiing Pullmonary Tubercullosiis iin Sputtum Smear Negattiive Pattiientts Muhammad Amir, Muhammad Iqbal, Ehsan Elahi, Muhammad Faraz, Owais Amjad Janjua,Muhammad Faizan Objective: To see diagnostic accuracy of GeneXpert MTB in diagnosing pulmonary tuberculosis in sputum smear negative patients. Study Design: Cross-sectional Study. Place and Duration of Study: Department of Pulmonology, Pakistan Emirates Military Hospital Rawalpindi, Pakistan from May to Oct 2024. Methodology: Patients having at least any of two clinical criteria and at least one radiological finding suspected of TB and were included. The clinical criteria comprised of intermittent fever or persistent cough for greater than 3 weeks, drenching night sweats for more than 2 weeks, HIV positive patients, weight loss greater 5% of body weight, and haemoptysis. The radiological criteria included cavitatory lesions, consolidation, pleural effusion or hilar adenopathy on chest radiographs. After initial history and investigations, all patients went through fiber optic bronchoscopy. The Lowenstein Jensen (LJ) medium was used for sample inoculation and incubated for 8 weeks. The GeneXpert MTB samples were processed as per manufacturer's specifications. Results: In this study, one hundred and twenty-two (n=122) patients median age of 46.00(28.75-59.25) years were included. The cough 95(77.87%), fever 79(64.75%) and weight loss 74(60.66%) were common symptoms respectively. The upper lung zone 84(68.85%) and middle lung zone 12(9.84%) were commonly involved. The GeneXpert MTB was reported high positive in 41(33.61%) patients. The GeneXpert MTB was found to be 92.64% sensitive, 85.71% specific and 90.98% accurate. The positive predictive and negative predictive values were 91.30% and 90.56% respectively. Conclusion: GeneXpert MTB is a reliable tool to test smear-negative patients suspected of tuberculosis. Prof Dr Muhammad Amir, Medicine, BUCM 2026-01-01T00:00:00Z http://hdl.handle.net/123456789/20945 Autism spectrum disorder trios from consanguineous populations are enriched for rare homozygous variants, identifying 32 new candidate genes Ricardo Harripaul, Ansa Rabia, Nasim Vasli, Anna Mikhailov, Ashlyn Rodrigues, Stephen F. Pastore, Tahir Muhammad, Thulasi Thiruvallur Madanagopal, Aisha Nasir Hashmi, Clinton Tran, Cassandra Stan, Katherine Aw, Clement C. Zai, Maleeha Azam, Saqib Mahmood, Abolfazl Heidari, Raheel Qamar, Leon French, Shreejoy Tripathy, Zehra Agha, Muhammad Iqbal, Majid Ghadami, Susan L. Santangelo, Bita Bozorgmehr, Laila Al Ayadhi, Roksana Sasanfar, Shazia Maqbool, Arsalan Hassan, James A. Knowles, Muhammad Ayub & John B. Vincent Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) that affects about 1 in 54 children worldwide, imposing enormous economic and socioemotional burden on families and communities. Genetic studies of ASD have identified de novo copy number variants (CNVs) and point mutations that contribute significantly to the genetic architecture, but the majority of these studies were conducted in populations unsuited for detecting autosomal recessive (AR) inheritance. However, several ASD studies in consanguineous populations point towards AR as an under-appreciated source of ASD variants. Methods: We used whole exome sequencing to look for rare variants for ASD in 115 proband-mother-father trios from populations with high rates of consanguinity, namely Pakistan, Iran, and Saudi Arabia. Consanguinity was assessed through microarray genotyping. Results: We report 77 candidate single nucleotide variants and indels, with 62% homozygous, 22% autosomal dominant/de novo , and 16% X-linked, in 55 trios. 56% of the variants were loss of function (LoF) or putative LoF (pLoF), and 44% nonsynonymous. We found an enrichment of homozygous variants, both in 16 genes previously reported for AR ASD and/or intellectual disability (ID) and 32 previously unreported AR candidate genes (including DAGLA, ENPP6 , FAXDC2 , ILDR2 , KSR2 , PKD1L1 , SCN10A, SHH, and SLC36A1). We also identified seven candidate homozygous exonic loss CNVs. ACCEPTED MANUSCRIPT ARTICLE IN PRESS ARTICLE IN PRESS Biallelic variants for autism…. Conclusions: The significant enrichment for homozygous variants among individuals with high Froh coefficients, compared with low Froh, either in known or candidate AR genes, confirms that genetic architecture for ASD among consanguineous populations is different to non-consanguineous populations. Assessment of consanguinity may assist in the genetic diagnostic process for ASD. Dr. Aisha Nasir Hashmi IPFP Fellow Research Cell BUCM 2026-01-01T00:00:00Z http://hdl.handle.net/123456789/20946 RELN biallelic variant as a candidate risk factor in a consanguineous Pakistani family with bipolar disorder and clinical heterogeneity Aisha Nasir Hashmi a, b,c, Ricardo S. Harripaul b,d, Tahir Muhammad b,d, Benjamin J. Lowther b, Anna Mikhailov b, Zehra Agha a,e, Raheel Qamar a,f, John B. Vincent b,d,g,*, Maleeha Azam Background: Bipolar disorder (BD) is highly heritable, polygenic, multifactorial, and has complex genetic heterogeneity. This study aimed to identify rare variants contributing to the aetiology of BD in a consanguineous family from Pakistan. Methods: Genome-wide SNP microarray and whole exome sequencing (WES) were used for variant identification in a large BD-affected consanguineous Pakistani family. Results: In family BF04, we identified three main regions of homozygosity-by-descent (HBD) over 1 Mb in length, by far the largest being a 43.6 Mb segment on chromosome 7, and, through WES analysis, found one promising novel homozygous variant in RELN (NM_005045; c.2090G>A; p.(Gly697Asp)), within this HBD region segregating in all the BD-affected members. Conclusion: Based on the clinical and genetic data, the present familial study revealed the plausible contribution of a novel variant of RELN in association with BD in the affected family. The present study's findings are valuable in understanding the genetic basis of the multifactorial phenotype BD and pave a better path for future functional studies. Dr. Aisha Nasir Hashmi IPFP Fellow Research Cell BUCM 2026-01-01T00:00:00Z http://hdl.handle.net/123456789/21095 Assessing Endobronchial Washing Mycobacterium Tuberculosis Gene Xpert's Role in Diagnosing Pulmonary Tuberculosis in Sputum Smear Negative Patients Muhammad Faizan, Muhammad Amir, Muhammad Iqbal, Ehsan Elahi, Muhammad Faraz, Owais Amjad Janjua Objective: To see diagnostic accuracy of GeneXpert MTB in diagnosing pulmonary tuberculosis in sputum smear negative patients. Study Design: Cross-sectional Study. Place and Duration of Study: Department of Pulmonology, Pakistan Emirates Military Hospital Rawalpindi, Pakistan from May to Oct 2024. Methodology: Patients having at least any of two clinical criteria and at least one radiological finding suspected of TB and were included. The clinical criteria comprised of intermittent fever or persistent cough for greater than 3 weeks, drenching night sweats for more than 2 weeks, HIV positive patients, weight loss greater 5% of body weight, and haemoptysis. The radiological criteria included cavitatory lesions, consolidation, pleural effusion or hilar adenopathy on chest radiographs. After initial history and investigations, all patients went through fiber optic bronchoscopy. The Lowenstein Jensen (LJ) medium was used for sample inoculation and incubated for 8 weeks. The GeneXpert MTB samples were processed as per manufacturer's specifications. Results: In this study, one hundred and twenty-two (n=122) patients median age of 46.00(28.75-59.25) years were included. The cough 95(77.87%), fever 79(64.75%) and weight loss 74(60.66%) were common symptoms respectively. The upper lung zone 84(68.85%) and middle lung zone 12(9.84%) were commonly involved. The GeneXpert MTB was reported high positive in 41(33.61%) patients. The GeneXpert MTB was found to be 92.64% sensitive, 85.71% specific and 90.98% accurate. The positive predictive and negative predictive values were 91.30% and 90.56% respectively. Conclusion: GeneXpert MTB is a reliable tool to test smear-negative patients suspected of tuberculosis. Prof Dr Muhammad Amir, Medicine, BUCM 2026-01-01T00:00:00Z