Pattern of Development and Sustainable Economic Growth In Pakistan: A Descriptive Analysis

Economic growth and development in Pakistan has always been erratic. This study attempts to examine possible causes and ramifications arising as a result. Major macroeconomic, social and environmental variables are examined using data from 1950 to 2013 and policy implications are chalked out. Literature shows that low savings and investment rates, budget deficit, institutional shortcomings, lack of human development and environmental degradation remains some of the major issues faced by the country. These factors together along with bad governance are considered as the major cause of unsustainable development. The descriptive analysis of the growth rates and averages of selected variables is conducted to study the pattern of economic growth and development. The study reveals that Pakistan has experienced unsustainable economic growth since its birth. Savings and investment has remained low and there is persistence of fiscal deficit. Furthermore trade deficit worsens the balance of payment situation. Investment in infrastructure, especially social infrastructure is inadequate and, hence human development is neglected. In addition, there is environmental degradation. Thus there is need for policies that encompass economic, social and environmental sectors. In other words policies should aim at achieving sustainable development

Pattern of Development and Sustainable Economic Growth In Pakistan: A Descriptive Analysis

Economic growth and development in Pakistan has always been erratic. This study attempts to examine possible causes and ramifications arising as a result. Major macroeconomic, social and environmental variables are examined using data from 1950 to 2013 and policy implications are chalked out. Literature shows that low savings and investment rates, budget deficit, institutional shortcomings, lack of human development and environmental degradation remains some of the major issues faced by the country. These factors together along with bad governance are considered as the major cause of unsustainable development. The descriptive analysis of the growth rates and averages of selected variables is conducted to study the pattern of economic growth and development. The study reveals that Pakistan has experienced unsustainable economic growth since its birth. Savings and investment has remained low and there is persistence of fiscal deficit. Furthermore trade deficit worsens the balance of payment situation. Investment in infrastructure, especially social infrastructure is inadequate and, hence human development is neglected. In addition, there is environmental degradation. Thus there is need for policies that encompass economic, social and environmental sectors. In other words policies should aim at achieving sustainable development

Assessing health-related quality of life, morbidity, and survival status for individuals with down syndrome in Pakistan (DS-Pak): Protocol for a web-based collaborative registry

Background: Down syndrome is the most common chromosomal disorder, with a global incidence of 1 in 700 live births. However, the true prevalence, associated morbidities, and health-related quality of life (HRQOL) of these individuals and their families are not well documented, especially in low- and middle-income countries such as Pakistan. Disease-specific documentation in the form of a collaborative registry is required to better understand this condition and the associated health outcomes. This protocol paper describes the aims and processes for developing the first comprehensive, web-based collaborative registry for Down syndrome in a Pakistani cohort.Objective: This study aims to assess the HRQOL, long-term survival, and morbidity of individuals with Down syndrome by using a web-based collaborative registry.Methods: The registry data collection will be conducted at the Aga Khan University Hospital and at the Karachi Down Syndrome Program. Data will be collected by in-person interviews or virtually via telephone or video interviews. Participants of any age and sex with Down syndrome (trisomy 21) will be recruited. After receiving informed consent and assent, a series of tablet-based questionnaires will be administered. The questionnaires aim to assess the sociodemographic background, clinical status, and HRQOL of the participants and their families. Data will be uploaded to a secure cloud server to allow for real-time access to participant responses by the clinicians to plan prompt interventions. Patient safety and confidentiality will be maintained by using multilayer encryption and unique coded patient identifiers. The collected data will be analyzed using IBM SPSS Statistics for Windows, Version 22.0 (IBM Corporation), with the mean and SD of continuous variables being reported. Categorical variables will be analyzed with their percentages being reported and with a P value cutoff of .05. Multivariate regression analysis will be conducted to identify predictors related to the HRQOL in patients with Down syndrome. Survival analysis will be reported using the Kaplan-Meier survival curves.Results: The web-based questionnaire is currently being finalized before the commencement of pilot testing. This project has not received funding at the moment (ethical review committee approval reference ID: 2020-3582-11145).Conclusions: This registry will allow for a comprehensive understanding of Down syndrome in low- and middle-income countries. This can provide the opportunity for data-informed interventions, which are tailored to the specific needs of this patient population and their families. Although this web-based registry is a proof of concept, it has the potential to be expanded to national, regional, and international levels.International registered report identifier (irrid): PRR1-10.2196/24901

eP271 - Disease-causing variants in hereditary neuromuscular disorder genes in an ethnically diverse Pakistani population - Experience from an Academic Medical Centre

Introduction: Neuromuscular disorders (NMD) are a broad group of clinically heterogeneous disorders, largely classified as neuropathies, myopathies, muscular dystrophies and myasthenic syndromes. These sub-classes are further divided into several subtypes, depending on the involved causative gene and affected proteins encoded by these genes. This heterogeneous group of disorders may be inherited in autosomal recessive, autosomal dominant and X-linked fashion, with over 500 implicated genes. (Ankala et al., 2014; Chae et al., 2015) The most commonly seen disorders in the pediatric age group are Spinal Muscular Atrophy and Dystronipathies, testing for which is locally available. Other disorders, which require more specialized diagnostic testing such as Next Generation Sequencing (NGS) are harder to diagnose.Objective: To study the clinical and genetic profiles of patients presenting for evaluation of a hereditary neuromuscular disorder, excluding SMA and Dystrophinopathies.Methods: This is a retrospective chart review of patients seen in the Neurology Clinic and referred to the Genetics Clinic with a suspected hereditary neuromuscular disorder, between 2015 and 2020 at the Aga Khan University Hospital, Karachi. The genetic testing for these patients included NGS based single gene sequencing as part of a research collaboration, NGS based multi-gene panel and whole exome sequencing at multiple CAP and CLIA accredited commercial genetics laboratories.Result and Discussion: A total of 75 pediatric and adult patients evaluated in our Neurology and Genetics Clinic went ahead with genetic testing. 39 tested positive showing Pathogenic or Likely Pathogenic variant[s] in genes associated with NMDs, matching both the clinical phenotype and the inheritance pattern. 29 patients had one or multiple variants of uncertain significance (VUS) and seven had a negative test result. From the 29 results harboring VUSs, 23 results remained truly inconclusive. However, we believe that six of the VUSs are actually disease causing, showing variant segregation with disease phenotype in the family, and following the disease inheritance pattern. Based on this, we showed how the diagnostic yield improved, from a 52% positive results to 60% positive results, based on the clinical interpretation of results, with the help of deep phenotyping and familial segregation studies. The result distribution and yield are summarized in Table 1. The results showed a spectrum of 26 different genes with distinct phenotypes of NMDs in 45 patients. The result distribution across the genotype is summarized in Figure 1. The three commonly seen phenotypes were, Limb Girdle Muscular Dystrophy (LMGD) characterized in 12 patients, followed by Collagenopathies characterized in seven patients and GNE-associated Myopathy in six patients. Delving into the positive result findings genotypes, the most common genes include, GNE (13%), DYSF (11%), COL6A2 (9%), FKTN (9%) and SGCB (7%), accounting for 49% (n = 22) positive results. In all four unrelated Fukuyama muscular dystrophy patients, FKTN variant: NM_001079802, Exon 9 c.920G\u3eA, p.Arg307Gln was found in a homozygous state. We also observed, that out of the six unrelated GNE associated myopathy patients, only GNE variant: NM_001128227.2, Exon 12 c.2179G\u3eA, p.Val727Met, was present in four patients, one harbored a homozygous variant and three harbored heterozygous variant, present alongside another diseasecause variant in GNE, in compound heterozygous state. These two variants may represent possible founder mutations in the Pakistani population.Conclusion: This data from a clinical setting in an ethnically diverse Pakistani patient population shows the genetic heterogeneity and the spectrum of associated phenotypes found in NMDs. 80% of the positive patients (36/45) of the patients had a diagnosis of an autosomal recessive NMD. It was also observed that 21% of the reported VUSs identified were likely to be disease-causing based on clinical interpretation, warranting the need for larger NMD focused studies in our population. Variants unique to our population need to be validated by further functional studies, to clarify which ones are indeed pathogenic. As our understanding of the underlying genetic etiology of NMD improves, precision medicine initiatives for treating NMDs will accelerate

eP069: Possible founder variant and spectrum of phenotypic manifestation of Fukuyama muscular dystrophy reported in four unrelated Pakistani families

Background: Monogenic Neuromuscular disorders (NMDs) are clinically and genetically heterogeneous group of disorders with about 500 associated genes. NMDs may be inherited in autosomal recessive, autosomal dominant and X-linked fashion. In the context of highly consanguineous Pakistani population, we expect the autosomal recessive NMDs to have a higher prevalence, compared to that seen in the populations with European ancestry. However, we do not have contextual ethno-specific genomics data for NMDs in Pakistani population. Next Generation Sequencing (NGS) has revolutionized the diagnostic practice for NMDs, having the ability to simultaneously capture and sequence multiple genes with disease-specific gene panels, sequence the coding portion of the human genome with whole exome sequencing (WES) or the entire genome with whole genome sequencing (WGS). With this becoming a clinical practice to integrate genomic testing in offering diagnosis; the challenge of diagnostic odyssey is diminishing. From the broad spectrum of hereditary NMDs, dystroglycanopathies are heterogenous group of disorders that typically manifest as limb-girdle muscular weakness. About 18 genes are now known to be associated with dystroglycanopathies, these genes encode proteins that function as a modulator for the binding of α-dystroglycan to the extracellular matrix ligands by glycosylation alternation. As a result of which, the structural integrity of the myocytes is disrupted, subsequently leading to muscle degeneration. FKTN is one of the genes associate with dystroglycanopathies, it encodes for a glycosyltransferase.Case presentation: We report four unrelated families of FKTN associated autosomal recessive Fukuyama Muscular Dystrophy (MIM:613152), from a diverse Pakistani patient population seen at a Tertiary Healthcare Centre, in Karachi Pakistan. All four patients harbored homozygous, well-established pathogenic missense variant, FKTN, NM_001079802.1:c.920G\u3eA (p.Arg307Gln), (gnomAD MAF 0.001204%, rs119463992). This variant has been previously reported in multiple Turkish families in homozygous state, and one multi-ethnic (half Jewish and half Indian) family with another variant found in compound heterozygous state. At large, about half of the cases of FKTN associated muscular dystrophy are reported with severe brain involvement; clinically manifesting as intellectual disability and seizure disorder. Consistent with the genotype-phenotype correlation, the protein-truncating variants result in a more severe phenotype than missense variants. In our reported cases, the variant has showed a spectrum of phenotype with variable symptom onset age (between age of 2-16 years); in patients belonging to different regions of the country. However, it is not reported to be associated with intellectual disability and seizure disorder. In the previously reported cases for this variant, cardiac involved has not been mentioned. Additionally, three out of four patients from our center, presented with dilated cardiomyopathy which progressive reduction in the left-ventricular ejection fraction (LV EF), while for the fourth patient an echocardiogram was not present. The clinical details from four, unrelated families are described in Table 1.Conclusion: We report four unrelated Pakistani families from ethnically diverse backgrounds, harboring similar pathogenic variant in FKTN, which is likely to be a founder variant, in South Asian and Middle Eastern ethnic groups. In these cases, the age of first symptom manifestation was variable, however all began with motor delays or difficulties. The dilated cardiomyopathy was a saliant feature, observed in three patients, that can lead to initiating cardiac screening in patients harboring this variant, at a younger age. Consistent with previous work, the symptom severity in the reported missense variant was mild, compared with protein-truncating variants, which is accompanied with severe brain involvement. As NMDs are further characterized in Pakistani populations, our knowledge of ethno-specific FTKN variants and their genotype-phenotype correlations will be better elucidated

Impact of Political Skill on Employee Outcomes with the Moderating Role of Perceived Organizational Politics

Purpose: Political skill has been attracting immense research attention in recent years. However, majority of the researches showed positive outcomes of political skill for employees. This research will provide new insights to literature through investigating the role of political skill in reducing negative behavioral outcomes of employees by developing job satisfaction to ultimately reduce turnover intention. Moreover, harmonizing effect of political skill in perceived organizational politics may enable employees to maintain job satisfaction and reduce turnover intention. Design/Methodology/Approach: Data were collected from 186 employees representing different sectors of Pakistani industry. Hayes (2013) moderated mediation analysis is used to analyze results. Findings: Study findings depict a significant relation between political skill and job satisfaction, which ultimately affect turnover intention. Furthermore, perceived organizational politics played a significant moderating role between political skill and job satisfaction. Implications/Originality/Value: The study is undertaken in a developing country which provides relevant conditions to investigate such a relationship. This study fills up a significant gap in the literature as there is scarce literature available that investigates the relationship between political skill and its outcomes, specifically in Pakistan

Novel homozygous TTI2 variant causing autosomal recessive syndromic intellectual disability and primary microcephaly from Pakistan: A case report (exome report)

We describe a male patient with a novel TTI2 variant, which has not been previously associated with a human phenotype. His features include intellectual disability, primary microcephaly, delayed psychomotor development, speech delay, short stature, dysmorphic facial features, esotropia, kyphoscoliosis, and behavior abnormalities (Figure). Next generation sequencing revealed autosomal recessive TTI2 variant with uncertain significance, denoted as c.21_22insAAGCGCTCTG (p.Glu8Lysfs × 12). TTI2 encodes a regulator of DNA damage response and helps maintain steady levels of the PIKK family of protein kinases. No disease-causing variants in other genes potentially linked to his clinical presentation were identified. We report a novel loss-of-function homozygous variant in TTI2 that leads to syndromic intellectual disability and primary microcephal

Clinical, pathological and molecular spectrum of patients with glycogen storage diseases in Pakistan

Objectives: Evaluation of clinical, biochemical and molecular analysis of Pakistani patients with hepatic GSDs.Methods: Medical charts, biochemical, histopathological and molecular results of patients with hepatic GSD were reviewed.Results: Out of 55 GSD patients, 41 (74.5%) were males and 14 (25.5%) were females with consanguinity in 50 (91%) patients. The median age of initial symptoms, clinic diagnosis and molecular diagnosis were 450 (IQR: 270-960), 1,095 (IQR: 510-1,825) and 1717 (IQR: 796-3,011) days, respectively. Molecular analysis and enzyme activity was available for 33 (60%) and two patients, respectively. GSD III (n=9) was most prevalent followed by GSD Ib (n=7), GSD IXc (n=6), GSD VI (n=4), GSD Ia (n=3), GSD XI (n=3), GSD IXb (n=2) and GSD IXa (n=1). In patients (n=33) who underwent molecular analysis; 19 different variants in eight genes associated with GSD were identified. We also report five novel variants, two in SLC37A4, one in AGL and two in PYGL contributing to the diagnosis of GSD Ib, GSD III and GSD VI, respectively.Conclusions: Fifty-five patients of GSDs in 26 families from a single care provider indicate a relatively high frequency of GSD in Pakistan, with multiple unrelated families harboring identical disease-causing variants, on molecular analysis, including two known pathogenic variants in SLC37A4 and PHKG2, and a novel variant in AGL

Prophylactic Risk-Reducing Mastectomy (PRRM): A set practice or catch-22 situation in LMIC. A single-centre prospective cohort study

Background: Pakistan\u27s hereditary breast cancer has a higher-than-average prevalence. Our acceptability of prophylactic risk-reducing mastectomy (PRRM) still needs to be determined, and genetic testing still needs to be offered to all eligible. The aim is to determine the number of women presenting to our centre who availed of PRRM after positive genetic tests and the main reasons restraining them from considering PRRM.Materials and methods: This study is a single-centre, prospective cohort. We collected data from 2017 to 2022 on BRCA1/2 and other (P/LP) gene-positive patients. Continuous variables are presented as means (±SD) and categorical variables in percentages, with a significant P-value of ≤ 0.05.Results: Out of 477 tested individuals, only 95(20.12%) had a positive result. BRCA1/2 was positive in 70 cases, while P/LP variants were in 24 cases. Only 32.6% of eligible families underwent genetic testing, with 54.8% positivity. Altogether, 92.6% of patients had BRCA1/2-related cancers. Only 25/95(26.3%) individuals availed of PRRM, the majority had contralateral risk-reducing mastectomy 68% with a 20% reconstruction rate. The main reasons to decline PRRM were false belief of not having any disease 57.44%, followed by family/spouse pressure 51%, body appearance/societal perception, fear of complications/quality of life and financial constraints.Conclusion: Genetic testing and its implications are still a grey area for LMICs, primarily due to the scarcity of centres offering genetic testing to eligible populations, followed by prevalent perceptions about prophylactic surgeries among the masses. Addressing relevant issues in LMICs is the need of time