An interesting case of infra-hisian block.

INTRODUCTION: The management of patients with conduction disease and supraventricular arrhythmias presents a multitude of clinical challenges.Intra-Hisian block, a condition characterized by delayed or blocked electrical conduction within the His bundle, can result in debilitating symptoms, such as syncope or presyncope. This case report aims to elucidate the diagnostic and therapeutic considerations that were taken in a patient who presented with recurrent syncopal episodes that corresponded to atrial flutter (AFL) and subsequently underwent cavotricuspid isthmus ablation. CASE PRESENTATION: A 65-year-old male with paroxysmal AFL and a pre-existing right bundle branch block and left anterior fascicular block (RBBB+LAFB) experienced recurrent syncopal episodes that were found to be correlated with AFL episodes. Following CTI ablation, an electrophysiology study (EPS) revealed a prolonged HV interval of 101ms, which indicated potential conduction abnormalities. With coronary sinus pacing, an intra-Hisian delay of 211ms was observed. During instances of atrioventricular block, intra-Hisian delay was evident on conducted beats, followed by intra-Hisian block on non-conducted beats. Ultimately, the patient's syncopal episodes prompted the placement of a dual-chamber pacemaker, which resulted in the resolution of symptoms. CONCLUSION: Intra-Hisian block is a condition that is often associated with delayed or blocked electrical conduction within the His bundle. When symptomatic, patients often present with syncope or presyncope. Etiologies of this condition include degenerative changes, myocardial infarction, autoimmune disorders, infections, medications, and more. This case emphasizes the importance of electrophysiology studies (EPS) in the diagnosis and management of patients with intra-Hisian block. Prompt intervention, such as the placement of a dual-chamber pacemaker, can alleviate symptoms and improve patient outcomes. Thus, clinical awareness and utilization of EPS can aid in accurate diagnosis and appropriate treatment selection for patients with conduction abnormalities and supraventricular arrhythmias.cuspid isthmus (CTI) ablation.

Genetic diagnosis in Sudanese and Tunisian families with syndromic intellectual disability through exome sequencing.

BACKGROUND: Intellectual disability is a form of neurodevelopmental disorders that begin in childhood and is characterized by substantial intellectual difficulties as well as difficulties in conceptual, social, and practical areas of living. Several genetic and nongenetic factors contribute to its development; however, its most severe forms are generally attributed to single-gene defects. High-throughput technologies and data sharing contributed to the diagnosis of hundreds of single-gene intellectual disability subtypes. METHOD: We applied exome sequencing to identify potential variants causing syndromic intellectual disability in six Sudanese patients from four unrelated families. Data sharing through the Varsome portal corroborated the diagnosis of one of these patients and a Tunisian patient investigated through exome sequencing. Sanger sequencing validated the identified variants and their segregation with the phenotypes in the five studied families. RESULT: We identified three pathogenic/likely pathogenic variants in CCDC82, ADAT3, and HUWE1 and variants of uncertain significance in HERC2 and ATP2B3. The patients with the CCDC82 variants had microcephaly and spasticity, two signs absent in the two previously reported families with CCDC82-related intellectual disability. CONCLUSION: In conclusion, we report new patients with pathogenic mutations in the genes CCDC82, ADAT3, and HUWE1. We also highlight the possibility of extending the CCDC82-linked phenotype to include spastic paraplegia and microcephaly.

Novel variants causing megalencephalic leukodystrophy in Sudanese families.

Mutations in MLC1 cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare form of leukodystrophy characterized by macrocephaly, epilepsy, spasticity, and slow mental deterioration. Genetic studies of MLC are lacking from many parts of the world, especially in Sub-Saharan Africa. Genomic DNA was extracted for 67 leukodystrophic patients from 43 Sudanese families. Mutations were screened using the NGS panel testing 139 leukodystrophies and leukoencephalopathies causing genes (NextSeq500 Illumina). Five homozygous MLC1 variants were discovered in seven patients from five distinct families, including three consanguineous families from the same region of Sudan. Three variants were missense (c.971 T > G, p.Ile324Ser; c.344 T > C, p.Phe115Ser; and c.881 C > T, p.Pro294Leu), one duplication (c.831_838dupATATCTGT, p.Ser280Tyrfs*8), and one synonymous/splicing-site mutation (c.762 C > T, p.Ser254). The segregation pattern was consistent with autosomal recessive inheritance. The clinical presentation and brain MRI of the seven affected patients were consistent with the diagnosis of MLC1. Due to the high frequency of distinct MLC1 mutations found in our leukodystrophic Sudanese families, we analyzed the coding sequence of MLC1 gene in 124 individuals from the Sudanese genome project in comparison with the 1000-genome project. We found that Sudan has the highest proportion of deleterious variants in MLC1 gene compared with other populations from the 1000-genome project.

Empirical Mode Decomposition-Based Feature Extraction for Environmental Sound Classification.

In environment sound classification, log Mel band energies (MBEs) are considered as the most successful and commonly used features for classification. The underlying algorithm, fast Fourier transform (FFT), is valid under certain restrictions. In this study, we address these limitations of Fourier transform and propose a new method to extract log Mel band energies using amplitude modulation and frequency modulation. We present a comparative study between traditionally used log Mel band energy features extracted by Fourier transform and log Mel band energy features extracted by our new approach. This approach is based on extracting log Mel band energies from estimation of instantaneous frequency (IF) and instantaneous amplitude (IA), which are used to construct a spectrogram. The estimation of IA and IF is made by associating empirical mode decomposition (EMD) with the Teager-Kaiser energy operator (TKEO) and the discrete energy separation algorithm. Later, Mel filter bank is applied to the estimated spectrogram to generate EMD-TKEO-based MBEs, or simply, EMD-MBEs. In addition, we employ the EMD method to remove signal trends from the original signal and generate another type of MBE, called S-MBEs, using FFT and a Mel filter bank. Four different datasets were utilised and convolutional neural networks (CNN) were trained using features extracted from Fourier transform-based MBEs (FFT-MBEs), EMD-MBEs, and S-MBEs. In addition, CNNs were trained with an aggregation of all three feature extraction techniques and a combination of FFT-MBEs and EMD-MBEs. Individually, FFT-MBEs achieved higher accuracy compared to EMD-MBEs and S-MBEs. In general, the system trained with the combination of all three features performed slightly better compared to the system trained with the three features separately.

Psychopathological symptoms as a common Risk Factor for Tinnitus distress and magnitude: A cross-sectional study.

OBJECTIVE: To examine the association of tinnitus distress, tinnitus magnitude and psychopathological symptoms among patients with ear-related problems. METHODS: The cross-sectional study was conducted from December 1, 2020, to June 30, 2021, at the Hearing and Balance Clinic, Rawalpindi, Pakistan, in collaboration with the National Institute of Psychology, Quaid-i-Azam University, Islamabad, Pakistan, and comprised adult tinnitus patients of either gender. All patients underwent ear examination and audiological evaluations for tinnitus matching. Psychological assessment was done using the Tinnitus Magnitude Index, the Tinnitus Reaction Questionnaire and the Symptoms Check List-90. Data was analysed using SPSS 21. RESULTS: Of the 159 subjects, 97(61%) were male and 62(39%) were females. The overall mean age was 47.94±17.47 years. Patients showed statistically significant tendency to develop psychopathological symptoms, including somatisation, phobic anxiety, depression and paranoid ideation (p<0.05). Additionally, significant gender differences were also observed (p<0.05). CONCLUSIONS: There was a high prevalence of tinnitus distress along with psychopathological symptoms among tinnitus patients.

An identical-by-descent novel splice-donor variant in PRUNE1 causes a neurodevelopmental syndrome with prominent dystonia in two consanguineous Sudanese families.

PRUNE1 is linked to a wide range of neurodevelopmental and neurodegenerative phenotypes. Multiple pathogenic missense and stop-gain PRUNE1 variants were identified in its DHH and DHHA2 phosphodiesterase domains. Conversely, a single splice alteration was previously reported. We investigated five patients from two unrelated consanguineous Sudanese families with an inherited severe neurodevelopmental disorder using whole-exome sequencing coupled with homozygosity mapping, segregation, and haplotype analysis. We identified a founder haplotype transmitting a homozygous canonical splice-donor variant (NM_021222.3:c.132+2T > C) in intron 2 of PRUNE1 segregated with the phenotype in all the patients. This splice variant possibly results in an in-frame deletion in the DHH domain or premature truncation of the protein. The phenotypes of the affected individuals showed phenotypic similarities characterized by remarkable pyramidal dysfunction and prominent extrapyramidal features (severe dystonia and bradykinesia). In conclusion, we identified a novel founder variant in PRUNE1 and corroborated abnormal splicing events as a disease mechanism in PRUNE1-related disorders. Given the phenotypes' consistency coupled with the founder effect, canonical and cryptic PRUNE1 splice-site variants should be carefully evaluated in patients presenting with prominent dystonia and pyramidal dysfunction.

A heterozygous mutation in the CCDC88C gene likely causes early-onset pure hereditary spastic paraplegia: a case report.

BACKGROUND: CCDC88C is a ubiquitously expressed protein with multiple functions, including roles in cell polarity and the development of dendrites in the nervous system. Bi-allelic mutations in the CCDC88C gene cause autosomal recessive congenital hydrocephalus (OMIM #236600). Studies recently linked heterozygous mutations in CCDC88C to the development of the late-onset spinocerebellar ataxia type 40 (OMIM #616053). CASE PRESENTATION: A 48-year-old Sudanese female presented with pure early onset hereditary spastic paraplegia. Exome sequencing, in-silico analysis, and Sanger sequencing identified the heterozygous NM_001080414.4:c.1993G > A (p.E665K) variant in CCDC88C as a potential cause of her illness. To explore the pathogenicity of the NM_001080414.4:c.1993G > A (p.E665K) variant, we expressed it in human embryonic kidney 293 cells and assessed its effects on apoptosis. In our experiment, NM_001080414.4:c.1993G > A (p.E665K) induced JNK hyper-phosphorylation and enhanced apoptosis. In contrast to previous reports, our patient developed neurological symptoms in early childhood and showed neither features of cerebellar ataxia, extrapyramidal signs, nor evidence of intellectual involvement. CONCLUSION: We, herein, heighlighted the possibility of extending the phenotype associated with variants in CCDC88C to include early-onset pure hereditary spastic paraplegia.

Genetic and expression deregulation of immunoregulatory genes in rheumatoid arthritis.

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases globally, and is an important public health concern, associating with early death and systemic complications. Although key development in RA treatment has already been made still RA affected individuals face comorbidity and disability. Therefore, there is a need to discover new risk factors in helping early diagnosis and treatment of RA. The present study is designed to assess the variations of Vitamin D receptor (VDR) and interleukin -6 (IL-6) in RA patients. Polymorphisms of said genes were calculated in 300 RA patients and 300 controls, using Tetra-ARMS polymerase chain reaction. Secondly, expression levels of selected genes were checked using the quantitative PCR (qPCR) and obtained results were evaluated using a different statistical test. Logistic regression analysis showed that frequency of mutant allele of VDR gene polymorphisms (rs11168268, OR = 4.84; 95% CI = 2.94-7.97; p = 0.0001; rs2248098, OR = 1.65; 95% CI = 1.07-2.54; p = 0.02) and IL-6 gene polymorphisms (rs184229712, OR = 2.47; 95% CI = 1.56-3.92, p = 0.0001; rs36215814, OR = 2.14; 95% CI = 1.30-3.53; p = 0.002) was observed significantly higher in RA patients vs controls. Expression analysis showed the significant upregulation of IL-6 (p < 0.0001) and downregulation of VDR gene (p < 0.0001) in RA cases vs controls. ROC curve analysis showed that downregulation of IL-6 (AUC = 0.86, p < 0.001) and upregulation of VDR (AUC = 0.77, p < 0.001) was act as the good diagnostic marker for detection/diagnosis of arthritis. In conclusions, data from the present study showed the significant involvement of VDR and IL-6 gene variations in RA pathogenesis.

A cross-sectional study to understand the pervasiveness of psychiatric features among tinnitus and vertigo patients.

OBJECTIVE: To identify the mental health problems among patients having symptoms of tinnitus and vertigo due to vestibulocochlear disturbances. METHODS: The cross-sectional study was conducted from May to September 2019 at the Hearts International Hospital and the Hearing and Balance Clinic, Rawalpindi, in collaboration with the Foundation University, Islamabad, and comprised vestibulocochlear disorder patients of either gender aged >18 years having chief symptoms of vertigo and tinnitus for at least the preceding 3 months. Psychiatric evaluation was conducted using the Tinnitus Handicap Inventory, the Dizziness Handicap Inventory and the Depression, Anxiety, Stress Scale. Audiological evaluations were carried out to gauge the severity of symptoms. Data was analysed using SPSS 20. RESULTS: Of the 202 subjects, 60(30%) were females and 142(70%) were males. Patients experiencing vertigo and tinnitus symptoms had a strong tendency to develop psychiatric problems (p<0.05). Significant differences were noted among male and female patients regarding the representation of psychiatric symptoms (p<0.05). CONCLUSION: Patients experiencing tinnitus and vertigo symptoms tended to have a deviant psychological profile analogous with other chronic diseases.

Self-harm behaviour, psychopathological distress and suicidal ideation in normal and deliberate self-harm outpatient's adults.

OBJECTIVE: To identify the association among suicidal ideation, deliberate self-harm, and psychopathological distress in normal and deliberate self-harm adults. METHODS: The cross-sectional study was conducted at the Department of Psychiatry, Military Hospital, Rawalpindi, Pakistan, from January to July 2017, and comprised deliberate self harm and normal adults aged 18-25 years. Psychiatric evaluation involved a semi-structured interview based on mental status examination. The self-harm tendency was assessed on the basis of self-harm inventory of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. Beck scale for suicide ideation and he depression anxiety and stress scale were also used for data collection. Data was analysed using SPSS 22. RESULTS: There were 200 subjects with a mean age of 20.89±9.06 years; 100(50%) each in deliberate self-harm and normal groups. Deliberate self-harm was significantly positively associated with suicidal ideation and mental health problems, including depression, anxiety and stress (p<0.05). Deliberate self-harm tendency was also positively associated with mental health problems in normal adults (p<0.05). Normal adults had higher level of mental health problems, such as depression and stress, compared to deliberate self harm adults (p<0.05). Adults having self-harm behaviour were more inclined to have suicidal ideation compared to normal adults behaviour (p<0.05). CONCLUSIONS: Deliberate self-harm was found to be strongly related to suicidal behaviour and mental health issues in both normal and deliberate self-harm adults.

Exploring UK medical school differences: the MedDifs study of selection, teaching, student and F1 perceptions, postgraduate outcomes and fitness to practise.

BACKGROUND: Medical schools differ, particularly in their teaching, but it is unclear whether such differences matter, although influential claims are often made. The Medical School Differences (MedDifs) study brings together a wide range of measures of UK medical schools, including postgraduate performance, fitness to practise issues, specialty choice, preparedness, satisfaction, teaching styles, entry criteria and institutional factors. METHOD: Aggregated data were collected for 50 measures across 29 UK medical schools. Data include institutional history (e.g. rate of production of hospital and GP specialists in the past), curricular influences (e.g. PBL schools, spend per student, staff-student ratio), selection measures (e.g. entry grades), teaching and assessment (e.g. traditional vs PBL, specialty teaching, self-regulated learning), student satisfaction, Foundation selection scores, Foundation satisfaction, postgraduate examination performance and fitness to practise (postgraduate progression, GMC sanctions). Six specialties (General Practice, Psychiatry, Anaesthetics, Obstetrics and Gynaecology, Internal Medicine, Surgery) were examined in more detail. RESULTS: Medical school differences are stable across time (median alpha = 0.835). The 50 measures were highly correlated, 395 (32.2%) of 1225 correlations being significant with p < 0.05, and 201 (16.4%) reached a Tukey-adjusted criterion of p < 0.0025. Problem-based learning (PBL) schools differ on many measures, including lower performance on postgraduate assessments. While these are in part explained by lower entry grades, a surprising finding is that schools such as PBL schools which reported greater student satisfaction with feedback also showed lower performance at postgraduate examinations. More medical school teaching of psychiatry, surgery and anaesthetics did not result in more specialist trainees. Schools that taught more general practice did have more graduates entering GP training, but those graduates performed less well in MRCGP examinations, the negative correlation resulting from numbers of GP trainees and exam outcomes being affected both by non-traditional teaching and by greater historical production of GPs. Postgraduate exam outcomes were also higher in schools with more self-regulated learning, but lower in larger medical schools. A path model for 29 measures found a complex causal nexus, most measures causing or being caused by other measures. Postgraduate exam performance was influenced by earlier attainment, at entry to Foundation and entry to medical school (the so-called academic backbone), and by self-regulated learning. Foundation measures of satisfaction, including preparedness, had no subsequent influence on outcomes. Fitness to practise issues were more frequent in schools producing more male graduates and more GPs. CONCLUSIONS: Medical schools differ in large numbers of ways that are causally interconnected. Differences between schools in postgraduate examination performance, training problems and GMC sanctions have important implications for the quality of patient care and patient safety.

The Analysis of Teaching of Medical Schools (AToMS) survey: an analysis of 47,258 timetabled teaching events in 25 UK medical schools relating to timing, duration, teaching formats, teaching content, and problem-based learning.

BACKGROUND: What subjects UK medical schools teach, what ways they teach subjects, and how much they teach those subjects is unclear. Whether teaching differences matter is a separate, important question. This study provides a detailed picture of timetabled undergraduate teaching activity at 25 UK medical schools, particularly in relation to problem-based learning (PBL). METHOD: The Analysis of Teaching of Medical Schools (AToMS) survey used detailed timetables provided by 25 schools with standard 5-year courses. Timetabled teaching events were coded in terms of course year, duration, teaching format, and teaching content. Ten schools used PBL. Teaching times from timetables were validated against two other studies that had assessed GP teaching and lecture, seminar, and tutorial times. RESULTS: A total of 47,258 timetabled teaching events in the academic year 2014/2015 were analysed, including SSCs (student-selected components) and elective studies. A typical UK medical student receives 3960 timetabled hours of teaching during their 5-year course. There was a clear difference between the initial 2 years which mostly contained basic medical science content and the later 3 years which mostly consisted of clinical teaching, although some clinical teaching occurs in the first 2 years. Medical schools differed in duration, format, and content of teaching. Two main factors underlay most of the variation between schools, Traditional vs PBL teaching and Structured vs Unstructured teaching. A curriculum map comparing medical schools was constructed using those factors. PBL schools differed on a number of measures, having more PBL teaching time, fewer lectures, more GP teaching, less surgery, less formal teaching of basic science, and more sessions with unspecified content. DISCUSSION: UK medical schools differ in both format and content of teaching. PBL and non-PBL schools clearly differ, albeit with substantial variation within groups, and overlap in the middle. The important question of whether differences in teaching matter in terms of outcomes is analysed in a companion study (MedDifs) which examines how teaching differences relate to university infrastructure, entry requirements, student perceptions, and outcomes in Foundation Programme and postgraduate training.

Using Volatile Organic Compounds to Investigate the Effect of Oral Iron Supplementation on the Human Intestinal Metabolome.

Patients with iron deficiency anaemia are treated with oral iron supplementation, which is known to cause gastrointestinal side effects by likely interacting with the gut microbiome. To better study this impact on the microbiome, we investigated oral iron-driven changes in volatile organic compounds (VOCs) in the faecal metabolome. Stool samples from patients with iron deficiency anaemia were collected pre- and post-treatment (n = 45 and 32, respectively). Faecal headspace gas analysis was performed by gas chromatography-mass spectrometry and the changes in VOCs determined. We found that the abundance of short-chain fatty acids and esters fell, while aldehydes increased, after treatment. These changes in pre- vs. post-iron VOCs resemble those reported when the gut is inflamed. Our study shows that iron changes the intestinal metabolome, we suggest by altering the structure of the gut microbial community.

Whey protein polymorphisms in Sudanese goat breeds.

The aim of the present study was to assess genetic variation that is characteristic for Sudanese goat breeds in the milk whey protein genes (LALBA and BLG). Four Sudanese goat breeds were screened for variability in LALBA and BLG genes at the DNA level by comparative sequencing of five animals per breed. Sixteen SNPs were identified in LALBA: seven in the upstream region, six synonymous, and three in the 3´-UTR. Three novel synonymous SNPs in exon 2 (ss5197800003, ss5197800012, and ss5197800004) were found in Nubian, Desert, and Nilotic, but not in Taggar goats. One SNP in the promoter of LALBA (rs642745519) modifies a predicted transcription factor binding site for Tcfe2a. The SNPs in the 3'-UTR (rs657915405, rs641559728, and rs664225585) affect predicted miRNA target sites. With respect to haplotypes in the exonic region, haplotype LALBA-A is most frequent in Nubian, Desert, and Nilotic goats, while haplotype LALBA-D is prevalent in Taggar goats. In BLG, 30 SNPs were detected: eight in the upstream gene region, two synonymous, 17 intronic, and three in the 3'-UTR. Among the 30 identified SNPs, 15 were novel. Four of these novel SNPs were located in the upstream gene region, one was synonymous, and ten were intronic. The novel synonymous SNP (ss5197800017), located in exon 2, was only found in Nubian and Nilotic goats. The SNPs ss5197800010 and rs635615192 in the promoter are located in predicted binding sites of transcription factors (M6097, Elk3, Elf5, and GABPA). Among seven haplotypes detected in the coding region, haplotype BLG-A is most frequent in Nubian and Nilotic goats while haplotype BLG-B is most frequent in Desert and Taggar goats. The high variability in regulatory gene regions among Sudanese goats could potentially affect the quality and yield of whey proteins in goat milk and provide a wide resource for genetic improvement of milk production and milk technology characteristics.

COVID-19 Pandemic and Impending Global Mental Health Implications.

The increase in organisms transference and infectious pandemics across the globe have been accelerated by an increase in travel, international exchange and global changes in earth's climate. COVID-19, a virus caused by the novel coronavirus that was initially identified on December 2019, in Wuhan city of China is currently affecting 146 territories, states and countries raising distress, panic and increasing anxiety in individuals exposed to the (actual or supposed) peril of the virus across the globe. Fundamentally, these concerns ascend with all infections, including those of flu and other agents, and the same worldwide safeguards are compulsory and suggested for protection and the prevention of further diffusion. However, media has underlined COVID-19 as rather an exclusive threat, which has added to panic and stress in masses which can lead to several mental health issues like anxiety, obsessive compulsive disorder and post-traumatic stress disorder which should be contained immediately in its initial phases.

Mycobacterium tuberculosis infection and resistance to rifampicin with GeneXpert®MTB/RIF: a single-center experience on bronchoalveolar lavage samples in renal failure patients.

Patients with end-stage renal disease (ESRD) are immunocompromised and are more at risk to develop and acquire Mycobacterium tuberculosis (MTB) infection. However, risk assessment is uncertain. The objective of current research was to study the frequency of MTB infection in ESRD patients . For this purpose, bronchoalveolar lavage (BAL) samples were evaluated for the presence of MTB by using GeneXpert®MTB/RIF test. We analysed 350 clinical samples of BAL collected from a tertiary care hospital in Pakistan, from September, 2015 to July, 2016. We performed the GeneXpert®test on each sample. According to our results prevalence of MTB was observed in 1.7% of bronchoalveolar lavage (BAL) samples taken from patients with chronic kidney diseases. All the positive samples were susceptible to rifampicin. There is a low prevalence of MTB infec tion (pulmonar y tuberculosis) in patients with chronic kidney disease in our setup. Suspected patients can be diagnosed by using GeneXpert®MTB/RIF testing on bronchoalveolar lavage samples.

Case report of a novel homozygous splice site mutation in PLA2G6 gene causing infantile neuroaxonal dystrophy in a Sudanese family.

BACKGROUND: Infantile neuroaxonal dystrophy (INAD) is a rare hereditary neurological disorder caused by mutations in PLA2G6. The disease commonly affects children below 3 years of age and presents with delay in motor skills, optic atrophy and progressive spastic tetraparesis. Studies of INAD in Africa are extremely rare, and genetic studies from Sub Saharan Africa are almost non-existent. CASE PRESENTATION: Two Sudanese siblings presented, at ages 18 and 24 months, with regression in both motor milestones and speech development and hyper-reflexia. Brain MRI showed bilateral and symmetrical T2/FLAIR hyperintense signal changes in periventricular areas and basal ganglia and mild cerebellar atrophy. Whole exome sequencing with confirmatory Sanger sequencing were performed for the two patients and healthy family members. A novel variant (NM_003560.2 c.1427 + 2 T > C) acting on a splice donor site and predicted to lead to skipping of exon 10 was found in PLA2G6. It was found in a homozygous state in the two patients and homozygous reference or heterozygous in five healthy family members. CONCLUSION: This variant has one very strong (loss of function mutation) and three supporting evidences for its pathogenicity (segregation with the disease, multiple computational evidence and specific patients' phenotype). Therefore this variant can be currently annotated as "pathogenic". This is the first study to report mutations in PLA2G6 gene in patients from Sudan.

Intra-familial phenotypic heterogeneity in a Sudanese family with DARS2-related leukoencephalopathy, brainstem and spinal cord involvement and lactate elevation: a case report.

BACKGROUND: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL, OMIM #611105) is a genetic disease of the central nervous system characterized by lower limb spasticity, cerebellar ataxia and involvement of the dorsal column. The disease is caused by mutations in the DARS2 gene but has never been reported in sub-Saharan Africa so far. CASE PRESENTATION: Two siblings, aged 18 years and 15 years, from a consanguineous family presented with pyramidal signs and symptoms since infancy and developmental delay. Whole exome sequencing of the proband identified two compound heterozygous variants (NM_018122.4:c.1762C > G and c.563G > A) in DARS2. Sanger sequencing confirmed the presence of the mutations and their segregation in trans in both patients and in their elder sister (aged 20 years), who showed only brisk reflexes and mild lower limb spasticity. Surprisingly, in contrast to her subtle clinical presentation, the elder sister had abnormal MRI features and serum lactate levels comparable to her ill sisters. CONCLUSION: This report illustrates intra-familial phenotypic variation in LBSL and provides an example of a marked dissociation between the clinical and radiological phenotypes of the disease. This may have implications for the detection of mutation carriers in LBSL.

Therapeutic interventions to lessen the psychosocial effect of vitiligo in children: A review.

Vitiligo commonly affects children, with half of affected individuals experiencing disease onset before the age of 20. Because childhood is a time of advancement in social and psychological development, understanding the extent of the effect of the disease and means of alleviation is crucial. Vitiligo has been shown to decrease children's quality of life, with greater distress in children with highly visible lesions and darker skin tones. This article reviews the literature regarding interventions that have been analyzed in children. Studies evaluating the effect of camouflage, cognitive behavioral therapy, psychological self-help tools, and support groups on the psychosocial aspects of vitiligo were included. The review highlights the ongoing need for studies to better understand the modalities described in this article, as well as others, such as skin dyes, bleaching creams, medical tattooing; week-long camps that cater to children with chronic skin disease; and biofeedback, that might have a role in preventing the psychosocial sequelae of childhood vitiligo.