College Of Medical Research Articles

The PS4-likelihood ratio calculator: flexible allocation of evidence weighting for case-control data in variant classification

BackgroundThe 2015 American College of Medical Genetics/Association of Molecular Pathology (ACMG/AMP) variant classification framework specifies that case-control observations can be scored as ‘strong’ evidence (PS4) towards pathogenicity.MethodsWe developed the PS4-likelihood...

Classroom to Clinic: Universities Need to Support The Next Generation of Clinical Academics

The General Medical Council’s current version of Outcomes for Doctors sets out three key areas of expertise for tomorrow’s doctors: professional values & behaviours, professional skills, and professional knowledge. (1) Each of these competencies further develops into numerous core skills every student should attain at medical school. While the learning outcomes set under Clinical Research & Scholarship (part of Outcome 3: Professional Knowledge) could usually be attained through numerous instances across a typical medical school curriculum, opportunities to put research skills into practice have remained relatively competitive and scarce. This represents an emerging challenge across the career spectrum, particularly in the UK as the Medical Schools Council warns that the NHS Long Term Workforce Plan 2031-32 could be jeopardised if the number of clinical academics is not maintained.(2) Facilitated by the impacts of an aging workforce alongside years of underinvestment – NHS trusts and medical schools need to work quickly to address barriers in training and retaining the next generation of clinical academics.(3) Clinical Academics are the foundation of the future of medical schools. However, much more must be done to introduce, facilitate, and encourage medical students to consider the option of training as a clinical academic. Investing in opportunities for medical students to get involved in research and teaching early on in their medical career, could be a solution not just to tackle this future workforce challenge but also to offer better career prospects. This is supported by evidence from research on matched-cohort studies conducted in Australia & New Zealand demonstrating an encouraging statistic independent of academic confounding variables. (4,5) Medical students who published research in medical student journals were significantly more likely to be associated with higher degree attainment, PubMed® indexed publications and in some cases, more likely to enter surgical training or their chosen specialty. However, getting involved in clinical research as a medical student remains challenging. Lack of opportunities, competitive funding calls, and fewer supervisors willing to take on the burden of training students are only some of the many barriers students currently face in getting involved. Recent results from a survey by the University of Glasgow’s Medical School demonstrated reassuring enthusiasm for a career in clinical research/teaching among a small sample size of 55 students. Commenting on these findings, Professor Iain McInnes, Head of the College of Medical, Veterinary and Life Sciences, said ‘.... supporting clinical academics at all stages of their career is a top priority for our college and this survey shows that the pipeline for the future of academia is in good health indeed!’. On the balance, the need of the hour must now focus on retaining this enthusiasm by investing in opportunities and offering pathways to ensure medical students can actively engage in academia. Several steps including enhancing funding, fostering stronger mentorship and networking opportunities, promoting interdisciplinary collaboration, and recognizing research efforts by medical students can go a long way in pursuing students to consider a rewarding career in clinical academia.

An Assessment of Predisposing Factors of Periodontitis in Individuals

Background: Periodontitis, characterized by clinical attachment loss (CAL), is a prevalent global oral health issue leading to tooth loss. Various predisposing factors such as smoking, dietary habits, stress, and oral trauma are implicated in its development. Understanding these factors is crucial for targeted interventions and improved periodontal health outcomes. Objective: To assess the predisposing factors of periodontitis in individuals. Methods: A descriptive cross-sectional study was conducted on 50 individuals visiting the College of Dentistry, Sharif Medical and Dental College, Lahore. Data were collected by measuring clinical attachment loss. Patients were classified based on CAL into mild, moderate, and severe periodontitis categories. The Chi-square test was used to analyze associations between periodontitis severity and factors like smoking duration, betel quid chewing, stress, oral trauma, and an unbalanced diet. Results: A significant association was found between smoking duration and periodontitis (p=0.04). Individuals with a smoking history of over five years had higher rates of severe (51%) and moderate (18.4%) periodontitis compared to those with a history of less than five years (8.2%). Betel quid chewing (p=0.254), stress (p=0.871), oral trauma (p=0.557), and an unbalanced diet (p=0.883) were not significantly associated with periodontitis. Conclusion: Severe periodontitis was more prevalent in individuals with a smoking history of over five years and those consuming an unhealthy diet. Moderate periodontitis was more common in individuals without a betel quid chewing habit. Mild periodontitis was observed in those reporting stress-related gum or tooth pain and those with a history of oral trauma.

Seroprevalence and detection of Toxoplasma gondii and Echinococcus granulosus in humans by indirect immunoglobulin G enzyme-linked immunosorbent assays in Baghdad

The present study was conducted from December 2021 until April 2023 at the College of Health and Medical, Al-Bayan University, Iraq, in Baghdad province, to detect the infection of Toxoplasma gondii in humans and identification by serological methods. Field studies were conducted from 1500 sera samples from hospitals and private medical laboratories. The sera samples were separated and examined by indirect ELISA IgG for the human kit to detect the infection with Toxoplasma gondii serologically. The serological results showed that 62% were positive. The present study recorded a high rate of infection in pregnant women at 70.4% (526/747) and then non-pregnant women at 53.6% (404/753). The serological results in males showed 57%, while the females showed 65.1%. It was noted non-significant difference. According to age groups 30-39 years, the high rate of infection was 90.2% (415/460), whereas the lowest infection among age groups < 20 years was 25.1% (83/330). However, serologically tested sera samples were positive for Echinococcus granuloses; 7.8% of 192 sera samples from humans were tested. Regarding the age group, the rate of infection was 10.2% (5\49) from <20 and >29 years, while from >30 to >39 years was 6.6% (3\45) and >40 years was 14% (7\50) with a high significant difference with Echinococcus. According to gender, the percentage of infestation in males was 5.7% out of (6\104) sera samples, while in females was 10.2% out of (9\88) sera samples with a highly significant difference (P≤0.01). Finally, regarding the months, the peak infection rate was recorded in March.

High-throughput functional mapping of variants in an arrhythmia gene, KCNE1, reveals novel biology

BackgroundKCNE1 encodes a 129-residue cardiac potassium channel (IKs) subunit. KCNE1 variants are associated with long QT syndrome and atrial fibrillation. However, most variants have insufficient evidence of clinical consequences and thus limited clinical utility.MethodsIn this study, we leveraged the power of variant effect mapping, which couples saturation mutagenesis with high-throughput sequencing, to ascertain the function of thousands of protein-coding KCNE1 variants.ResultsWe comprehensively assayed KCNE1 variant cell surface expression (2554/2709 possible single-amino-acid variants) and function (2534 variants). Our study identified 470 loss- or partial loss-of-surface expression and 574 loss- or partial loss-of-function variants. Of the 574 loss- or partial loss-of-function variants, 152 (26.5%) had reduced cell surface expression, indicating that most functionally deleterious variants affect channel gating. Nonsense variants at residues 56–104 generally had WT-like trafficking scores but decreased functional scores, indicating that the latter half of the protein is dispensable for protein trafficking but essential for channel function. 22 of the 30 KCNE1 residues (73%) highly intolerant of variation (with > 70% loss-of-function variants) were in predicted close contact with binding partners KCNQ1 or calmodulin. Our functional assay data were consistent with gold standard electrophysiological data (ρ = − 0.64), population and patient cohorts (32/38 presumed benign or pathogenic variants with consistent scores), and computational predictors (ρ = − 0.62). Our data provide moderate-strength evidence for the American College of Medical Genetics/Association of Molecular Pathology functional criteria for benign and pathogenic variants.ConclusionsComprehensive variant effect maps of KCNE1 can both provide insight into IKs channel biology and help reclassify variants of uncertain significance.

Complex genotype–phenotype correlation of MYH11: new insights from monozygotic twins with highly variable expressivity and outcomes

BackgroundThoracic aortic aneurysm/dissection (TAAD) and patent ductus arteriosus (PDA) are serious autosomal-dominant diseases affecting the cardiovascular system. They are mainly caused by variants in the MYH11 gene, which encodes the heavy chain of myosin 11. The aim of this study was to evaluate the genotype–phenotype correlation of MYH11 from a distinctive perspective based on a pair of monozygotic twins.MethodsThe detailed phenotypic characteristics of the monozygotic twins from the early fetal stage to the infancy stage were traced and compared with each other and with those of previously documented cases. Whole-exome and Sanger sequencing techniques were used to identify and validate the candidate variants, facilitating the analysis of the genotype–phenotype correlation of MYH11.ResultsThe monozygotic twins were premature and presented with PDA, pulmonary hypoplasia, and pulmonary hypertension. The proband developed heart and brain abnormalities during the fetal stage and died at 18 days after birth, whereas his sibling was discharged after being cured and developed normally post follow-up. A novel variant c.766 A > G p. (Ile256Val) in MYH11 (NM_002474.2) was identified in the monozygotic twins and classified as a likely pathogenic variant according to the American College of Medical Genetics/Association for Molecular Pathology guidelines. Reviewing the reported cases (n = 102) showed that the penetrance of MYH11 was 82.35%, and the most common feature was TAAD (41.18%), followed by PDA (22.55%), compound TAAD and PDA (9.80%), and other vascular abnormalities (8.82%). The constituent ratios of null variants among the cases with TAAD (8.60%), PDA (43.8%), or compound TAAD and PDA (28.6%) were significantly different (P = 0.01). Further pairwise comparison of the ratios among these groups showed that there were significant differences between the TAAD and PDA groups (P = 0.006).ConclusionThis study expands the mutational spectrum of MYH11 and provides new insights into the genotype–phenotype correlation of MYH11 based on the monozygotic twins with variable clinical features and outcomes, indicating that cryptic modifiers and complex mechanisms beside the genetic variants may be involved in the condition.

Effect of Periodontal Scaling in Patients Undergoing Orthodontic Treatment on General Oral and Periodontal Health

Background: Orthodontic treatments, while improving dental alignment and facial aesthetics, significantly complicate oral hygiene management due to the fixed nature of orthodontic appliances. This study investigates the potential benefits of periodontal scaling in mitigating the adverse effects on oral and periodontal health among orthodontic patients. Objective: To evaluate the impact of periodontal scaling on the general oral and periodontal health of patients undergoing orthodontic treatment. Methods: This descriptive cross-sectional study included 50 patients from the College of Dentistry, Sharif Medical and Dental College, Lahore. Conducted from April 2023 to April 2024, the study utilized a questionnaire to collect demographic data and information about the patients’ last dental scaling. The Community Periodontal Index for Treatment Needs (CPITN) and the Decayed, Missing, Filled Teeth Index (DMFT) assessed the periodontal and general oral health. Results: The correlations between the time since the last scaling and general oral health (DMFT score: p=0.950) and periodontal health (CPITN: p=0.635) were not statistically significant. Higher DMFT scores were noted in patients who last had scaling over a year ago (30%), followed by those never scaled (26%). Pocket depths of 6mm were solely observed in unscaled patients. Conclusion: The incidence of decayed, missing, and filled teeth, as well as deeper pocket depths, were notably higher in orthodontic patients who had not received scaling in over a year or never at all, emphasizing the necessity of regular periodontal care.

ClinGen variant curation expert panel recommendations for classification of variants in GAMT, GATM and SLC6A8 for cerebral creatine deficiency syndromes

Cerebral creatine deficiency syndromes (CCDS) are inherited metabolic phenotypes of creatine synthesis and transport. There are two enzyme deficiencies, guanidinoacetate methyltransferase (GAMT), encoded by GAMT and arginine-glycine amidinotransferase (AGAT), encoded by GATM, which are involved in the synthesis of creatine. After synthesis, creatine is taken up by a sodium-dependent membrane bound creatine transporter (CRTR), encoded by SLC6A8, into all organs. Creatine uptake is very important especially in high energy demanding organs such as the brain, and muscle. To classify the pathogenicity of variants in GAMT, GATM, and SLC6A8, we developed the CCDS Variant Curation Expert Panel (VCEP) in 2018, supported by The Clinical Genome Resource (ClinGen), a National Institutes of Health (NIH)-funded resource. We developed disease-specific variant classification guidelines for GAMT-, GATM-, and SLC6A8-related CCDS, adapted from the American College of Medical Genetics/Association of Molecular Pathology (ACMG/AMP) variant interpretation guidelines. We applied specific variant classification guidelines to 30 pilot variants in each of the three genes that have variants associated with CCDS. Our CCDS VCEP was approved by the ClinGen Sequence Variant Interpretation Working Group (SVI WG) and Clinical Domain Oversight Committee in July 2022. We curated 181 variants including 72 variants in GAMT, 45 variants in GATM, and 64 variants in SLC6A8 and submitted these classifications to ClinVar, a public variant database supported by the National Center for Biotechnology Information. Missense variants were the most common variant type in all three genes. We submitted 32 new variants and reclassified 34 variants with conflicting interpretations. We report specific phenotype (PP4) using a points system based on the urine and plasma guanidinoacetate and creatine levels, brain magnetic resonance spectroscopy (MRS) creatine level, and enzyme activity or creatine uptake in fibroblasts ranging from PP4, PP4_Moderate and PP4_Strong. Our CCDS VCEP is one of the first panels applying disease specific variant classification algorithms for an X-linked disease. The availability of these guidelines and classifications can guide molecular genetics and genomic laboratories and health care providers to assess the molecular diagnosis of individuals with a CCDS phenotype.

Spectrum of LYST mutations in Chediak-Higashi syndrome: a report of novel variants and a comprehensive review of the literature

IntroductionChediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterised by partial oculocutaneous albinism, a bleeding diathesis, immunological dysfunction and neurological impairment. Bi-allelic loss-of-function variants in LYST cause CHS. LYST...

The impact of damaging epilepsy and cardiac genetic variant burden in sudden death in the young

BackgroundSudden unexpected death in children is a tragic event. Understanding the genetics of sudden death in the young (SDY) enables family counseling and cascade screening. The objective of this study was to characterize genetic variation in an SDY cohort using whole genome sequencing.MethodsThe SDY Case Registry is a National Institutes of Health/Centers for Disease Control and Prevention surveillance effort to discern the prevalence, causes, and risk factors for SDY. The SDY Case Registry prospectively collected clinical data and DNA biospecimens from SDY cases < 20 years of age. SDY cases were collected from medical examiner and coroner offices spanning 13 US jurisdictions from 2015 to 2019. The cohort included 211 children (median age 0.33 year; range 0–20 years), determined to have died suddenly and unexpectedly and from whom DNA biospecimens for DNA extractions and next-of-kin consent were ascertained. A control cohort consisted of 211 randomly sampled, sex- and ancestry-matched individuals from the 1000 Genomes Project. Genetic variation was evaluated in epilepsy, cardiomyopathy, and arrhythmia genes in the SDY and control cohorts. American College of Medical Genetics/Genomics guidelines were used to classify variants as pathogenic or likely pathogenic. Additionally, pathogenic and likely pathogenic genetic variation was identified using a Bayesian-based artificial intelligence (AI) tool.ResultsThe SDY cohort was 43% European, 29% African, 3% Asian, 16% Hispanic, and 9% with mixed ancestries and 39% female. Six percent of the cohort was found to harbor a pathogenic or likely pathogenic genetic variant in an epilepsy, cardiomyopathy, or arrhythmia gene. The genomes of SDY cases, but not controls, were enriched for rare, potentially damaging variants in epilepsy, cardiomyopathy, and arrhythmia-related genes. A greater number of rare epilepsy genetic variants correlated with younger age at death.ConclusionsWhile damaging cardiomyopathy and arrhythmia genes are recognized contributors to SDY, we also observed an enrichment in epilepsy-related genes in the SDY cohort and a correlation between rare epilepsy variation and younger age at death. These findings emphasize the importance of considering epilepsy genes when evaluating SDY.

Novel WFS1 variants are associated with different diabetes phenotypes.

The WFS1 gene encodes the protein wolframin, which is crucial for maintaining endoplasmic reticulum homeostasis. Variants in this gene are predominantly associated with Wolfram syndrome and have been implicated in other disorders such as diabetes mellitus and psychiatric diseases, which increases the rate of clinical misdiagnosis. Patients were diagnosed with early-onset unclassified diabetes according to their clinical and laboratory data. We performed whole-exome sequencing (WES) in 165 patients, interpreting variants according to the American College of Medical Genetics/Association for Molecular Pathology (ACMG/AMP) 2015 guidelines. Variant verification was done by Sanger sequencing. In vitro experiments were conducted to evaluate the effects of WFS1 compound heterozygous variants. We identified WFS1 compound heterozygous variants (p.A214fs*74/p.F329I and p.I427S/p.I304T) in two patients with Wolfram Syndrome-Like disorders (WSLD). Both WFS1 compound heterozygous variants were associated with increased ER stress, reduced cell viability, and decreased SERCA2b mRNA levels. Additionally, pathogenic or likely pathogenic WFS1 heterozygous variants were identified in the other three patients. Our results underscore the importance of early genetic testing for diagnosing young-onset diabetes and highlight the clinical relevance of WFS1 variants in increasing ER stress and reducing cell viability. Incorporating these genetic insights into clinical practice can reduce misdiagnoses and improve treatment strategies for related disorders.

Prevalence of Obsessive Compulsive Symptoms in Medical and Dental Practitioners with Respect to Gender

Obsessive compulsive disorder (OCD) comprises of mental images that provoke anxiety and fear and are recurrent. Objective: To find the prevalence of OCD symptoms in medical doctors and dentists with respect to gender. Methods: The study design was cross sectional comparative. It was conducted in College of Dentistry, Sharif Medical and Dental College Lahore. All practitioners irrespective of their age and gender were included in the study. Individuals practiced in a clinic or hospital for less than 6 months were excluded from the study. Obsessive compulsive inventory scale was used for data collection. Results: Gender of medical doctors and dentists and the symptom of washing (p=0.335, p=0.760 respectively), obsessing (p=0.131, p=0.476 respectively), checking (p=0.620, p=1.000 respectively) and neutralizing (p=0.294, p=1.000 respectively) was not significantly associated. The association between the symptom of ordering and gender of medical practitioners (p=0.05) was statistically significant. The association between gender of dental practitioners with hoarding (p=0.188), ordering (p=0.713) and doubting (p=1.000) was non-significant. Conclusions: Among the medical practitioners the symptoms of washing, obsessing, checking and neutralizing were higher in males as compared to the females. Among the dental practitioners the symptom of washing, obsessing and neutralizing were more prevalent in males while the symptom of checking was more prevalent in females. The symptoms of hoarding, ordering and doubting were more prevalent in males in comparison to female medical practitioners. Among the dental practitioners where the prevalence of hoarding was higher in the males while that of ordering and doubting was higher in the females.

An Assessment of Radiolucencies Associated with Second Molar Adjacent Impacted Third Molar in Left in Comparison to Right Mandible

Mandibular third molars are the most prevalently impacted teeth in the oral cavity. These partially impacted teeth in addition to being the root cause of pathologies in the third molar themselves also pose problems for their adjacent second molars. The second molars adjacent impacted third molars lead to the development of various pathologies that manifest themselves as radiolucencies on radiographic evaluation. Objective: To evaluate the radiolucencies of the left mandible's second molar next to the impacted third molar in comparison with right mandible. Methods: A cross-sectional and descriptive study was undertaken on patients visiting College of Dentistry, Sharif Medical and Dental College (SMDC). A total of 385 OPGs were assessed for the presence of radiolucencies in the second molars adjacent impacted mandibular third molars from December 2020 to February 2021. Results: The association between the availability of periapical radiolucencies (p≤0.001) and radiolucencies due to caries and external resorption in second molar in the right and left mandible (p≤0.001) was significant. Conclusion: It was seen that majority of the cases with periapical radiolucency in the right mandible also had them left mandible as well but most of the cases with caries and external resorption in the right mandible did not have them in left mandible as well.

How human genetic context can inform pathogenicity classification: FGFR1 variation in idiopathic hypogonadotropic hypogonadism.

Precision medicine requires precise genetic variant interpretation, yet many disease-associated genes have unresolved variants of unknown significance (VUS). We analyzed variants in a well-studied gene, FGFR1, a common cause of Idiopathic Hypogonadotropic Hypogonadism (IHH) and examined whether regional genetic enrichment of missense variants could improve variant classification. FGFR1 rare sequence variants (RSVs) were examined in a large cohort to (i) define regional genetic enrichment, (ii) determine pathogenicity based on the American College of Medical Genetics/Association for Molecular Pathology (ACMG/AMP) variant classification framework, and (iii) characterize the phenotype of FGFR1 variant carriers by variant classification. A total of 143 FGFR1 RSVs were identified in 175 IHH probands (n = 95 missense, n = 48 protein-truncating variants). FGFR1 missense RSVs showed regional enrichment across biologically well-defined domains: D1, D2, D3, and TK domains and linker regions (D2-D3, TM-TK). Using these defined regions of enrichment to augment the ACMG/AMP classification reclassifies 37% (20/54) of FGFR1 missense VUS as pathogenic or likely pathogenic (PLP). Non-proband carriers of FGFR1 missense VUS variants that were reclassified as PLP were more likely to express IHH or IHH-associated phenotypes [anosmia or delayed puberty] than non-proband carriers of FGFR1 missense variants that remained as VUS (76.9% vs 34.7%, p = 0.035). Using the largest cohort of FGFR1 variant carriers, we show that integration of regional genetic enrichment as moderate evidence for pathogenicity improves the classification of VUS and that reclassified variants correlated with phenotypic expressivity. The addition of regional genetic enrichment to the ACMG/AMP guidelines may improve clinical variant interpretation.

Impact of Personality Trait of Emotional Stability on Oral Parafunctional Habits

OBJECTIVES To find the impact of emotional stability on oral parafunctional habits. METHODOLOGY A Cross-sectional descriptive study was conducted at the College of Dentistry, Sharif Medical and Dental College, Lahore, over five months, from July to November 2021. Data was collected using a medical questionnaire and a ten-item personality inventory scale (TIPI). The medical questionnaire comprised two sections with 11 items. The first section had six demographic statements, including age, gender, marital status, occupation, educational level and medical condition. The second section consisted of a pre-validated parafunctional habits questionnaire. RESULTSThere was a non-significant difference in the scores of the personality trait of emotional stability across categories of oral parafunctional habits of nail-biting (p=0.093), tooth grinding (p=0.192), tooth clenching (p=0.055), biting on hard objects (p=0.17) and chewing gum (p=0.116). CONCLUSION Emotional stability was most prevalent in individuals who denied having the habit of nail-biting, teeth grinding, tooth clenching and biting hard objects but neither agreed nor disagreed with having the habit of chewing gum.

Inter-Rater Reliability Regarding the Radiolucencies Associated with the Second Molar Adjacent an Impacted Third Mandibular Molar

OBJECTIVES To assess the inter-rater reliability regarding the radiolucencies associated with a second molar adjacent to an impacted third molar. METHODOLOGY A cross-sectional comparative study was conducted in the College of Dentistry, Sharif Medical and Dental College, Lahore, in which dentists from four different specialities, namely; Oral Pathology, Endodontics, Prosthodontics and Oral and Maxillofacial surgery, were included as raters. 21 Orthopantomograms were assigned to each rater for assessing radiolucencies associated with a second molar adjacent to an impacted third molar. RESULTSThe level of agreement regarding the radiolucencies associated with the second molar observed on the Orthopantomograms between rater 1 with rater 2 (κ=0.158., p=0.036) and rater 1 with rater 3 (κ=0.139, p=1.000) was very weak but was fair between rater1 and 4 (κ=0.271, p=0.200). CONCLUSION The only radiolucency that rater one observed was external root resorption. Rater 2 identified one case of radiolucency as dental caries and another as caries and periapical radiolucency that were identified by Rater 1 as external resorption; hence they had a weak agreement between Rater 1 and Rater 2 regarding the radiolucencies associated with second molars. Rater 3 identified radiolucencies owing to caries which were reported to be radiolucency due to external resorption by rater 1, and this agreement was weak. Most radiolucencies determined by rater 1 as external resorption were reported to be external resorption by rater 4, resulting in a fair agreement between rater 1 and 4.

HEalth And Dementia outcomes following Traumatic Brain Injury (HEAD-TBI): protocol for a retrospective cohort study

BackgroundIt is estimated that by 2050 the global incidence of dementia will have exceeded 152 million. At present, there are no effective therapies for dementia, with a focus in research...

O-303 Contribution of targeted sequencing for genetic diagnosis of premature ovarian insufficiency in clinical practice

Abstract Study question What is the diagnostic yield of custom designed gene panel for patients with premature ovarian insufficiency (POI)? Summary answer The diagnostic yield of our POI gene panel (POIGP) is 7.3% What is known already POI is a specific female syndrome with a high clinical and genetic heterogeneity. It is characterized by a premature exhaustion of the ovarian function and infertility and affects approximately 1% of women. POI can be related to genetic factors which include chromosomal abnormalities, FMR1 premutation and rare variants in numerous genes. The advent of high throughput sequencing methods has led to the identification of an increasing number of variants implicated in the development of POI over the last decades. However, POI etiologies still remain undetermined in the majority of cases. Study design, size, duration An observational analytic cohort study of 150 patients presenting idiopathic POI (normal karyotype, absence of FMR1 premutation, absence of adrenal and/or ovarian antibodies) recruited prospectively at three Belgian academic and university hospitals between 2016 and 2021. Participants/materials, setting, methods Patients were included if they experienced POI, as defined by ESHRE guidelines on POI (2016). POI genes included in the panel were selected from PubMed using different key words mainly premature ovarian insufficiency, gonadal dysgenesis, hypergonadotropic hypogonadism, ovarian failure and genetics. The panel included 156 genes, variants were filtered based on allele frequency (≤1%) in latest available population databases and classified according to ACMG/AMP (American College of Medical Genetics/Association for Molecular Pathology) guidelines 2015. Main results and the role of chance Our analysis revealed a potential causative variant for 11 patients in the following genes: MEIOB, BMP4, CFTR, FANCA, FSHR, FANCG, MLH1, MRPS22 and STARD9. This means that the diagnostic yield of our POI gene panel (POIGP) is 7.3%. Patients were mainly Caucasian (63%), North African (17%) and sub-Saharan African (13%). They presented primary amenorrhea in 14.7% of cases. Consanguinity and/or a family history of POI or early menopause in 28% of cases. Mean patient’s age (years) at POI diagnosis was 28.9± 8.5 (mean ± SD). The overall mean coverage was 229X, and more than 95% of the target exome was represented with more than 30-fold coverage. Limitations, reasons for caution The present study was limited to monogenic etiologies of POI, potential oligogenic causes have not been searched. Functional studies and/or family segregation were not performed for the identified variants. Wider implications of the findings Our findings show the importance of targeted next generation sequencing in clinical practice and highlight the limit of our current genetic knowledge in the field of POI. A regular update of genes included in POIGP will improve its diagnostic yield. Trial registration number P2016/196/CCB B406201628264

Prevalence of Personality Traits in Undergraduate Dental Students with Respect to Gender

OBJECTIVES To study the personality traits of undergraduate dental students with respect to gender. METHODOLOGY A Cross-sectional descriptive study was conducted at the College of Dentistry, Sharif Medical and Dental College, Lahore, over 5 months, from July to November 2021. Data was collected using the Ten Item Personality Inventory scale which was a pre-validated questionnaire.RESULTS There was a statistically significant association between gender and the personality of trait of emotional stability (p=0.017). There was a non-significant association between gender and the personality traits of extraversion (p=0.273), agreeableness (p=0.416), conscientiousness (p=0.147) and openness to experience (p=0.184).CONCLUSION The personality traits of extraversion, agreeableness, conscientiousness and openness to experience were more prevalent in the females in comparison to the males.

An Analysis of Coexistence of Multiple Oral Parafunctional Habits in Extraverts

Objective: To assess the presence and coexistence of multiple oral parafunctional habits in individuals with extravert personality type Methodology: A Cross-sectional descriptive study was conducted at the College of Dentistry, Sharif Medical and Dental College, Lahore, over 5 months, from July to November 2021. Data was collected using medical questionnaire and ten item personality inventory scale (TIPI). Results: There was significant association in the coexistence of parafunctional habit of nail biting with tooth clenching (p≤0.001), tooth grinding(p≤0.001), biting hard objects (p≤0.001) and chewing gum (p=0.027). Practical Implication: This study will help dental practitioners use personality assessment as an effective and important tool to find the propensity of an individual for development of oral parafunctional habits. In this way they will be able to provide timely treatment and counselling to the individuals before their dental health deteriorates due the development of oral parafunctional habits. Conclusion: The oral parafunctional habits found to coexist the most with nail biting habit was tooth grinding followed by biting hard objects, chewing gum and tooth clenching. Keywords: Extraverts, Oral parafunctional habits, Ten Item Inventory Scale, Nail Biting