Perception of Medical students regarding lectures

Objective: To assess the interest of medical students in lectures.Methodology: This prospective study was conducted in four different medical colleges of Pakistan from 1st January till 30th March 2015. Total of 600 students were included in this study. Data collection procedure used was questionnaire which contained both open and close ended questions. Written consent was taken from all the participants & permission was taken from the ethical review board of college. SPSS 15 was used to analyze the data.Results: Almost 59% of students in our study consider the lecture as uninteresting tool in medical studies and only 46% consider lecture as essential part of their education during the college timings. Good part of our study is majority of the students managed to reach lecture in time. 77.25% students consider use multimedia helpful during lectures.Conclusion: According to our study, students consider lecture as not very important and uninteresting part of medical education

Perception of Medical students regarding lectures

Objective: To assess the interest of medical students in lectures.Methodology: This prospective study was conducted in four different medical colleges of Pakistan from 1st January till 30th March 2015. Total of 600 students were included in this study. Data collection procedure used was questionnaire which contained both open and close ended questions. Written consent was taken from all the participants & permission was taken from the ethical review board of college. SPSS 15 was used to analyze the data.Results: Almost 59% of students in our study consider the lecture as uninteresting tool in medical studies and only 46% consider lecture as essential part of their education during the college timings. Good part of our study is majority of the students managed to reach lecture in time. 77.25% students consider use multimedia helpful during lectures.Conclusion: According to our study, students consider lecture as not very important and uninteresting part of medical education

Whole exome sequencing identifies a novel mutation in ASPM and ultra-rare mutation in CDK5RAP2 causing primary microcephaly in consanguineous Pakistani families

Background & objectives: Primary Microcephaly (MCPH) is a rare neurogenetic disease, manifesting congenitally reduced head circumference and non-progressive intellectual disability (ID). To date, twenty-eight genes with biallelic mutations have been reported for this disorder. The study aimed for molecular genetic characterization of Pakistani families segregating MCPH. Methods: We studied two unrelated consanguineous families (family A and B) presenting \u3e2 patients with diagnostic symptoms of MCPH, born to asymptomatic parents. We employed whole-exome sequencing (WES) of probands to find putative causal mutations. The candidate variants were further confirmed and analyzed for co-segregation by Sanger sequencing of all available members of each family. This study was conducted at Government College University, Faisalabad, Pakistan, and Cologne Center for Genomics (CCG), University of Cologne, Germany; during 2017-2020. Results: We identified a novel homozygous variant c.10097_10098delGA, p.(Gly3366Glufs*19) in exon 26 of ASPM gene in family A which presents with moderate intellectual disability, speech impairment, visual abnormalities, seizures, and ptyalism. Family B was found to segregate nonsense, homozygous variant c.448C\u3eT p.(Arg150*) in CDK5RAP2. The patients also exhibited mild to severe seizures without ptyalism that has not been previously reported in patients with mutations in the CDK5RAP2 gene. Conclusion: We report a novel mutation in ASPM and ultra-rare mutation in the CDK5RAP2 gene, both causing primary microcephaly. The study expands the mutational spectrum of the ASPM gene to 212, and also adds to the clinical spectrum of CDK5RAP2 mutations. It also demonstrated the utility of WES in the investigation and genetic diagnosis of genetically heterogeneous disorders like MCPH. These findings would aid in diagnostic and preventive strategies including carrier screening, cascade testing, and genetic counselling

Epidemiological Data of Neurological Disorders in Pakistan and Neighboring Countries: A Review

Neurological disorders are the impairments of nervous system and are an important and growing cause of morbidity, mortality, and disability. In addition to health costs, those suffering from these conditions are also frequently victimized of stigmatization and discrimination. Stigmatization further minimizes the patients\u27 access to treatment and social activities. These disorders, therefore, require special attention particularly in developing countries where unfortunately, the burden of these disorders remains largely unrecognized. Moreover, the burden imposed by such chronic neurological conditions in general can be expected to be particularly devastating in poor populations. These conditions are emerging as severe public health concerns in the developing countries due to the facts such as unawareness, Illiteracy, large numbers of people who are untreated, and unavailability of inexpensive but effective interventions. Regrettably, reliable population-based data from developing countries including Pakistan on the epidemiology of neurological disorders are extremely limited. Although, some information on epidemiological aspects of neurological diseases are available from some developing countries (Pakistan, Iran, India, Sri Lanka, Saudi Arabia and China) but disease prevalence and pattern are based on geographical, social, cultural, religious, and ethnic factors. In this review, w e critically analyzed data of 209 studies regarding the burden and prevalence of hypertension, depression, Stroke, Alzheimer\u27s disease (AD), epilepsy, and Parkinson\u27s disease (PD) in Pakistan and neighboring countries

Neurological disorder burden in Faisalabad, Punjab-Pakistan:data from the major tertiary carecenters of the city

The burden of neurological disorders (NDs) in developing countries is 4-5%, compared to 10-11% in developed countries. This burden is rising in developing countries due to prolonged life expectancy, improved health facilities, easy access to diagnostic facilities, and a trend in urbanization. There is inadequate data about the epidemiology of major NDs in Pakistan and most available information are hospital-based estimations or physicians’ collected data

Tumor Necrosis Factor Alpha SNP Variant in Promoter Region G308a, cause Preeclampsia during Pregnancy in Pakistani Women, A Case Control Study

Preeclampsia (PE) is a very common critical condition during pregnancy. As PE is a highrisk condition during pregnancy, occurring in 25% of all pregnancies, worldwide. In women with PE there is an increase in hypertension and albuminuria. Elevated blood pressure can be life-threatening after 20th week of pregnancy. Single nucleotide variation in gene sequence can be disease causing, among these pathogenic SNPs, a variant in TNF-α, G308A is analyzed in many studies as a causative variant to cause preeclampsia. In this case control study fifty patients and fifty healthy individuals were enrolled for analysis of TNF-α promoter region SNP G308A from Jinnah hospital, Lahore, Pakistan. The genotyping of TNF-α (G308A) rs1800629 polymorphisms was performed by PCR-RFLP method. Data analysis was performed by using SNPStats, statistical tool. The mean age of all patients and controls were calculated, 24.4 ± 6.6 and 25.1 ± 5.3 years, respectively. The frequency of G308A polymorphism was more prevalent in the case group, in association with control group (p<0.001). There was a significant correlation between inflammation promoting genotypes of TNF-α and PE. It can be warily concluded that: TNF- α (G-308A) polymorphism can be reflected as a marker of predisposition to preeclampsia in our population

Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies

Purpose: We aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition.Methods: We performed a detailed clinical characterization of 19 individuals from nine unrelated, consanguineous families with a neurodevelopmental disorder. We used genome/exome sequencing approaches, linkage and cosegregation analyses to identify disease-causing variants, and we performed three-dimensional molecular in silico analysis to predict causality of variants where applicable.Results: In all affected individuals who presented with a neurodevelopmental syndrome with progressive microcephaly, seizures, and intellectual disability we identified biallelic disease-causing variants in Protocadherin-gamma-C4 (PCDHGC4). Five variants were predicted to induce premature protein truncation leading to a loss of PCDHGC4 function. The three detected missense variants were located in extracellular cadherin (EC) domains EC5 and EC6 of PCDHGC4, and in silico analysis of the affected residues showed that two of these substitutions were predicted to influence the Ca2+-binding affinity, which is essential for multimerization of the protein, whereas the third missense variant directly influenced the cis-dimerization interface of PCDHGC4.Conclusion: We show that biallelic variants in PCDHGC4 are causing a novel autosomal recessive neurodevelopmental disorder and link PCDHGC4 as a member of the clustered PCDH family to a Mendelian disorder in humans

Modifier genes in microcephaly: A report on WDR62, CEP63, RAD50 and PCNT variants exacerbating disease caused by biallelic mutations of ASPM and CENPJ

Congenital microcephaly is the clinical presentation of significantly reduced head circumference at birth. It manifests as both non-syndromic-microcephaly primary hereditary (MCPH)-and syndromic forms and shows considerable inter- and intrafamilial variability. It has been hypothesized that additional genetic variants may be responsible for this variability, but data are sparse. We have conducted deep phenotyping and genotyping of five Pakistani multiplex families with either MCPH (n = 3) or Seckel syndrome (n = 2). In addition to homozygous causal variants in ASPM or CENPJ, we discovered additional heterozygous modifier variants in WDR62, CEP63, RAD50 and PCNT-genes already known to be associated with neurological disorders. MCPH patients carrying an additional heterozygous modifier variant showed more severe phenotypic features. Likewise, the phenotype of Seckel syndrome caused by a novel CENPJ variant was aggravated to microcephalic osteodysplastic primordial dwarfism type II (MOPDII) in conjunction with an additional PCNT variant. We show that the CENPJ missense variant impairs splicing and decreases protein expression. We also observed centrosome amplification errors in patient cells, which were twofold higher in MOPDII as compared to Seckel cells. Taken together, these observations advocate for consideration of additional variants in related genes for their role in modifying the expressivity of the phenotype and need to be considered in genetic counseling and risk assessment

A novel missense mutation in TNNI3K causes recessively inherited cardiac conduction disease in a consanguineous Pakistani family

Cardiac conduction disease (CCD), which causes altered electrical impulse propagation in the heart, is a life-threatening condition with high morbidity and mortality. It exhibits genetic and clinical heterogeneity with diverse pathomechanisms, but in most cases, it disrupts the synchronous activity of impulse-generating nodes and impulse-conduction underlying the normal heartbeat. In this study, we investigated a consanguineous Pakistani family comprised of four patients with CCD. We applied whole exome sequencing (WES) and co-segregation analysis, which identified a novel homozygous missense mutation (c.1531T\u3eC;(p.Ser511Pro)) in the highly conserved kinase domain of the cardiac troponin I-interacting kinase (TNNI3K) encoding gene. The behaviors of mutant and native TNNI3K were compared by performing all-atom long-term molecular dynamics simulations, which revealed changes at the protein surface and in the hydrogen bond network. Furthermore, intra and intermolecular interaction analyses revealed that p.Ser511Pro causes structural variation in the ATP-binding pocket and the homodimer interface. These findings suggest p.Ser511Pro to be a pathogenic variant. Our study provides insights into how the variant perturbs the TNNI3K structure-function relationship, leading to a disease state. This is the first report of a recessive mutation in TNNI3K and the first mutation in this gene identified in the Pakistani population