FRMD7 Gene Alterations in a Pakistani Family Associated with Congenital Idiopathic Nystagmus.

Congenital idiopathic nystagmus (CIN) is an oculomotor disorder characterized by repetitive and rapid involuntary movement of the eye that usually develops in the first six months after birth. Unlike other forms of nystagmus, CIN is widely associated with mutations in the FRMD7 gene. This study involves the molecular genetic analysis of a consanguineous Pakistani family with individuals suffering from CIN to undermine any potential pathogenic mutations. Blood samples were taken from affected and normal individuals of the family. Genomic DNA was extracted using an in-organic method. Whole Exome Sequencing (WES) and analysis were performed to find any mutations in the causative gene. To validate the existence and co-segregation of the FRMD7 gene variant found using WES, sanger sequencing was also carried out using primers that targeted all of the FRMD7 coding exons. Additionally, the pathogenicity of the identified variant was assessed using different bioinformatic tools. The WES results identified a novel nonsense mutation in the FRMD7 (c.443T>A; p. Leu148 *) gene in affected individuals from the Pakistani family, with CIN resulting in a premature termination codon, further resulting in the formation of a destabilized protein structure that was incomplete. Co-segregation analysis revealed that affected males are hemizygous for the mutated allele c.443T>A; p. Leu148 * and the affected mother is heterozygous. Overall, such molecular genetic studies expand our current knowledge of the mutations associated with the FRMD7 gene in Pakistani families with CIN and significantly enhance our understanding of the molecular mechanisms involved in genetic disorders.

Estimation of real COVID-19 cases in India during the first wave.

In 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread across the world within a few months. The SARS-CoV-2 pandemic has had a devastating effect on humanity, with social and economic consequences. The continents of Europe and America have been hit the hardest. However, there has also been a huge loss of life in India, with the country having the fourth highest number of total deaths worldwide. Nevertheless, the infection and death rates per million and the case fatality ratio in India are substantially lower than those in many developed nations. Several explanations for this have been proposed, including genetics. Mathematical modelling has suggested that the actual number of infections is much higher than the number of reported cases. Therefore, to understand the dynamics of actual infection and the population-level immunity against SARS-CoV-2, a serosurvey (antibody testing) was performed among 2301 individuals in urban regions of 14 districts in six states of India. A notable outcome of this study was that a large proportion of the Indian population had an asymptomatic SARS-CoV-2 infection. The real infection rate in India was several fold higher than the reported number of cases. Therefore, a large number of people in the country have developed SARS-CoV-2-specific antibodies. In this survey, the seroprevalence (frequency antibody-positive) varied between 0.01 (95% CI 0.002-0.054) and 0.477 (95% CI 0.392-0.563), suggesting a high variability in viral transmission between the states and the possibility of future waves. In this study population, the frequency of asymptomatic infection was highest in the younger age groups. It was also found that the numbers of cases reported by the government were several-fold lower than the real incidence of infection. It is likely that the high number of asymptomatic cases was the main driver of this discrepancy.

Homocysteine and vitamin B12: Other causes of neural tube defects in Eastern Uttar Pradesh and Western Bihar population.

BACKGROUND: Neural tube defects (NTDs) are congenital malformations with an incidence of 1-10/1000 live births. Homocysteine and vitamin B12 metabolism have been shown to be associated with NTDs. AIM: To investigate the status of maternal and neonate's folic acid, homocysteine, and vitamin B12 levels and their association with the risk of development of NTDs in the population of Eastern Uttar Pradeshand Western Bihar, India. MATERIALS AND METHODS: This study is a cross-sectional, retrospective study where 96 mothers who either had a first NTD child or had a history of NTD child in the family and 126 neonates with spina bifida were recruited during the period 2012-2015. Eighty-four control mothers whose previous and current pregnancies were normal, and 87 control neonates who had no defects and were within the same age range as the NTD affected neonates, recruited from the department of pediatric surgery, were enrolled in the study. Plasma concentrations of folic acid, vitamin B12, and homocysteine were compared between cases and controls. RESULTS: The folic acid level in the mothers and neonates was within the normal limit. A significant increase in the level of homocysteine in mothers with affected pregnancy and in neonate cases in comparison to control mothers was obseved. Further, a significant decrease in the level of vitamin B12 in mothers with NTD neonates and in the affected neonates was noted. A negative correlation was found between homocysteine and vitamin B12 levels in case and control mothers. CONCLUSION: A correlation of an increase in serum homocysteine with a decrease in vitamin B12 was seen in mothers of neonates with NTD. A similar observation as made in the neonates with NTDs. It may be suggested that maternal decrease in vitamin B12, in mothers who have normal folic acid may be associated with NTD in their children.

A prospective pilot study on serum cleaved tau protein as a neurological marker in severe traumatic brain injury.

OBJECTIVE: Neurotrauma has been labelled as a "silent epidemic" affecting both the developed and the developing nations. To date, no single brain-specific biomarker has been unanimously accepted for routine clinical use in TBI. Our study aims to determine the correlation of "cleaved-tau protein" in severe traumatic brain injury (TBI) with Glasgow Coma Scale (GCS) at the time of admission, mode of injury, CT findings and outcome at discharge. METHODS: The study has been approved by the institutional ethical committee. 40 cases with severe TBI and 40 randomly selected healthy controls were included in this prospective study. Venous blood samples were collected and serum cleaved tau protein levels were measured and correlated with gender, mode of injury, CT findings GCS score and GOS score at discharge. RESULTS: In the severe TBI group, the mean serum cleaved tau protein levels in males were 91.65 ± 41.34 pg/ml (mean ± S.D.), and females were 104.43 ± 53.08 pg/ml (mean ± S.D.), (p = 0.27). Mean serum C-tau level in study group was 95.48 ± 44.87 pg/ml (range 36.44-192.34), 95% C.I. (81.13-109.83) and in controls was 33.82 ± 13.65 pg/ml (range 2.48-66.54), 95% C.I. (29.46-38.19) (p < 0.001). The distribution of serum C-tau was in severe TBI group varied in all categories of GCS at 0th day (p < 0.001). Serum cleaved tau protein levels in the good outcome group were 74.26 ± 25.43 pg/ml (mean ± S.D.), range 36.44-144.54, 95% C.I. (63.52-85.00) and the poor-outcome group were 127.32 ± 49.40 pg/ml, range 66.65-192.34, 95% C.I. (100.99-153.64) (p = 0.001). CONCLUSION: In severe TBI, serum cleaved tau protein levels were significantly higher as compared to the controls in this prospective study. However, results of this study are preliminary in nature and there is a need to undertake larger prospective studies to reach a definitive conclusion.

High incidence of neural tube defects in Northern part of India.

BACKGROUND: In the absence of primary care and prevailing associated social stigma, many patients of neural tube defects (NTDs) from remote areas die without getting any treatment. The high number of such untreated cases and unregistered deaths in these areas made us ponders to the fact that tertiary care center-based studies do not represent the true incidence of NTDs. MATERIALS AND METHODS: We did a population-based survey for NTDs births of rural areas from Jaunpur to Ghazipur district in Eastern Uttar Pradesh. These districts are among the least developed areas of Northern India in Uttar Pradesh among other 17. RESULTS: The data show an incidence of 7.48 per 1000 live births. CONCLUSION: Besides of unawareness regarding periconceptional folate supplementation, intensive effort is required to design adequately powered studies to search other key factors responsible for high prevalence of NTDs.

Epidemiology of Congenital Heart Disease in India.

OBJECTIVE: Congenital heart defects (CHDs) affect a large number of newborns and account for a high proportion of infant mortality worldwide. There are regional differences in the prevalence and distribution pattern of CHDs. The aim of this study is to estimate the distribution pattern and prevalence of CHDs among the population of north-central India and to compare the results with studies in other regions of the country to get an overview of prevalence of CHDs in India. DESIGN: We carried out a prospective study in the outpatient department of a tertiary care referral center in north-central India. This study was carried out from January 2011 to April 2014, with 34 517 individuals being recruited for the study. All patients were examined by chest x-ray, electrocardiogram, and 2D echocardiography. Prevalence rate per 1000 individuals examined was calculated. Relative frequencies of individual CHD types as a proportion of total CHDs were also calculated. RESULTS: Out of 34 517 individuals examined, 661 were diagnosed with CHDs, giving a prevalence of 19.14 per 1000 individuals. The most common defect was ventricular septal defect (33%), followed by atrial septal defect (19%) and tetralogy of Fallot (16%). The majority of CHD cases (58%) diagnosed were between 0 and 5 years of age. The prevalence of CHDs in adults was 2.4 per 1000 individuals in this cohort, with atrial septal defect (44.5%) being the most frequent defect. CONCLUSION: The prevalence of CHDs in our cohort was high, possibly because of the power of the diagnostic methods we used and the inclusion of all age groups. Adults with CHDs may significantly contribute to the prevalence of CHDs in the next generation, and this needs to be considered when estimating prevalence rates. Although several small regional studies have been carried out in India, there is an urgent need to establish a nationwide registry/database for congenital heart defects.