Publications
At MedGenome, we are deeply focused on continuous innovation, and publishing our findings for the larger benefit of the genetic testing community. Read through our publications for details of our latest work.
Optimization and Validation of a Harmonized Protocol for Generating Therapeutic-Grade Dendritic Cells in a Randomized Phase II Clinical Trial, Using Two Varied Antigenic Sources.
Abstract:Autologous dendritic cell (DC)-based immunotherapy is a cell-based advanced therapy medicinal product (ATMP) that was first introduced more than three decades ago. In the current study, our objective was to establish a harmonized protocol using two varied antigenic sources and a good manufacturing practice (GMP)-compliant, manual method for generating clinical-grade DCs at a limited-resource academic setting. After obtaining ethical committee-approved…
Acute lymphoblastic leukemia with myeloid mutations is a high-risk disease associated with clonal hematopoiesis
Abstract:Myeloid neoplasms arise from pre-existing clonal hematopoiesis (CH), however the role of CH in pathogenesis of ALL is unknown. We found that 18% of adult ALL cases harbored TP53, and 16% had myeloid CH-associated gene mutations. ALL with myeloid mutations (MyM) had distinct genetic and clinical characteristics, associated with inferior survival. By using single cell proteogenomic analysis, we demonstrated that…
Diagnostic exome identifies a novel PRKG2 mutation in a proband with skeletal dysplasia
Abstract:This graphic abstract combines pedigree, dysmorphology features, radiographs, and the PRKG2 protein domain, specifically the CNB-A regulatory domain, which harbors a mutation resulting in premature protein termination.
The Genetic Drivers Of Juvenile, Young, And Early-Onset Parkinson’s Disease In India
Abstract:Recent studies have advanced our understanding of the genetic drivers of Parkinson’s disease (PD). Rare variants in more than 20 genes are considered causal for PD, and the latest PD genome-wide association study (GWAS) identified 90 independent risk loci. However, there remains a gap in our understanding of PD genetics outside of the European populations in which the vast majority…
Clinical Utility of Proband Only Clinical Exome Sequencing in Neurodevelopmental Disorders
Abstract:Chromosomal microarray is recommended as the first line of investigation in neurodevelopmental disorders (NDDs). However, advances in next-generation sequencing have unraveled more than 900 genes associated with NDDs, thus improving the genetic diagnosis. Therefore, this study was conducted to explore the utility of clinical exome sequencing (CES) in NDDs from a tertiary care centre in India. A retrospective observational analysis…
Kindler syndrome with a novel mutation and a rare gynaecological complication
Abstract:Kindler syndrome is a rare genodermatosis characterized by mechanical skin fragility, acral blisters, photosensitivity, poikiloderma, skin atrophy and mucosal inflammation.1 It is considered a subtype of inherited epidermolysis bullosa. The disease is inherited in an autosomal recessive pattern with the parents of the affected individuals being obligate heterozygotes.2 We report a case of a patient with Kinder syndrome with a giant myometrial…
Identification of a shared, common haplotype segregating with an SGCB c.544 T > G mutation in Indian patients affected with sarcoglycanopathy
Abstract:Sarcoglycanopathy is the most frequent form of autosomal recessive limb-girdle muscular dystrophies caused by mutations in SGCB gene encoding beta-sarcoglycan proteins. In this study, we describe a shared, common haplotype co-segregating in 14 sarcoglycanopathy cases from 13 unrelated families from south Indian region with the likely pathogenic homozygous mutation c.544 T > G (p.Thr182Pro) in SGCB.
Detection of 22q11.2 deletion syndrome by single-nucleotide polymorphism based non-invasive prenatal test
Abstract:Non-invasive prenatal test (NIPT) has become a popular screening test worldwide for screening common trisomies. In addition, the test can also sex chromosomal aneuploidies (SCAs) with similar sensitivity. In recent years, the scope of NIPT has extended to screen pregnancies for clinically significant microdeletions (MDs), rare autosomal aneuploidies, and subchromosomal abnormalities.
South Asian medical cohorts reveal strong founder effects and high rates of homozygosity
Abstract:The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927…
Genotype-phenotype correlation and natural history study of dysferlinopathy: a single-centre experience from India
Abstract:Dysferlinopathies are a group of limb-girdle muscular dystrophies causing significant disability in the young population. There is a need for studies on large cohorts to describe the clinical, genotypic and natural history in our subcontinent. To describe and correlate the clinical, genetic profile and natural history of genetically confirmed dysferlinopathies.
Exome sequencing and microarray identified a novel large exonic deletion in SYT2 gene in an ultra-rare case with recessive CMS type 7.
Abstract:Congenital myasthenic syndromes (CMSs) are a diverse group of diseases that have an underlying defect in transmission of signals from nerve cells to muscles that lead to muscular weakness. A 13-year-old male child born of consanguineous parents with profound motor developmental delay and normal cognition was referred to us.
Near-chromosomal de novo assembly of Bengal tiger genome reveals genetic hallmarks of apex predation
Abstract:The tiger, a poster child for conservation, remains an endangered apex predator. Continued survival and recovery will require a comprehensive understanding of genetic diversity and the use of such information for population management.
A novel compound heterozygous BEST1 gene mutation in two siblings causing autosomal recessive bestrophinopathy
Abstract:To describe the clinical features, imaging characteristics, and genetic test results associated with a novel compound heterozygous mutation of the BEST1 gene in two siblings with autosomal recessive bestrophinopathy. Methods Two siblings underwent a complete ophthalmic examination, including dilated fundus
Prenatal Diagnosis for Primary Immunodeficiency Disorders-An Overview of the Indian Scenario
Abstract:Prenatal Diagnosis (PND) forms an important part of primary preventive management for families having a child affected with primary immunodeficiency. Although individually sparse, collectively this group of genetic disorders represents a significant burden of disease. This paper discusses the prenatal services available for affected families at various centers across the country and the challenges and ethical considerations associated with genetic…
Clinico-epidemiological and genomic profile of first Zika Virus outbreak in India at Jaipur city of Rajasthan state
Abstract:First Zika virus (ZIKV) positive case from North India was detected on routine surveillance of Dengue-Like Illness in an 85-year old female. Objective of the study was to conduct an investigation for epidemiological, clinical and genomic analysis of first ZIKV outbreak in Rajasthan, North India and enhance routine ZIKV surveillance.
Think of SCA45 in Late-Onset Familial Ataxias: The First Report from the Indian Subcontinent with a Novel Variant
Abstract:An 82-year-old male patient presented with insidious onset and slowly progressive imbalance during walking over a period of the last 20 years. He also suffered from recurrent bouts of bullous pemphigoid for the last 30 years and developed hearing difficulty for the last 3 years. He had a strong family history of late onset gait imbalance involving his mother, four of his elder…
Multiomic analysis of papillary thyroid cancers identifies BAIAP2L1-BRAF fusion and requirement of TRIM25, PDE5A and PKCδ for tumorigenesis
Abstract:Papillary thyroid carcinoma (PTC) is one of the most common forms of thyroid cancer with a cure rate of over 90% after surgery. However, aggressive forms may still occur, and personalized therapeutic strategies are increasingly required. Methods We performed integrated genomic and proteomic analysis of PTC tumor samples from patients who did not harbor BRAF or RAS mutations.
Galectin antagonist use in mild cases of SARS-CoV-2; pilot feasibility randomised, open label, controlled trial
Abstract:Importance Novel SARS-CoV-2 virus has infected nearly half a billion people across the world and is highly contagious. There is a need for a novel mechanism to block viral entry and stop its replication. Background Spike protein N terminal domain (NTD) of the novel SARS-CoV-2 is essential for viral entry and replication in human cell.
Maternal opioid use disorder: Placental transcriptome analysis for neonatal opioid withdrawal syndrome
Abstract:Excessive prenatal opioid exposure may lead to the development of Neonatal Opioid Withdrawal Syndrome (NOWS). RNA-seq was done on 64 formalin-fixed paraffin-embedded placental tissue samples from 32 mothers with opioid use disorder, with newborns with NOWS that required treatment, and 32 prenatally unexposed controls. We identified 93 differentially expressed genes in the placentas of infants with NOWS compared to unexposed…
Novel Consensus Splice Site Pathogenic Variation in THOC2 Gene Leads to Recurrent Arthrogryposis Multiplex Congenita Phenotype: A Case Report
Abstract:The THOC2 gene encodes THO complex subunit 2, a subunit of the Transcription-Export (TREX) complex which binds specifically to splice messenger ribonucleic acid (mRNAs) to facilitate mRNA export. Mutations in the THOC2 gene have been described to lead to X-linked mental retardation syndrome type 12/35 (XLMR-12/35) (MIM#300957).
Drug-resistant ‘Non-Lesional’ Visual Sensitive Epilepsies of Childhood – Electroclinical Phenotype-Genotype Associations
Abstract:Sporadic nonlesional intractable visual-sensitive epilepsies of childhood represent a challenging subset of epilepsies in terms of management and prognostication given a propensity to evolve as epileptic encephalopathy. Objective: To study the genetic heterogeneity of drug-resistant visual sensitive epilepsy of childhood.
NGS-Based Expanded Carrier Screening For Genetic Disorders In North Indian Population Reveals Unexpected Results – A Pilot Study
Abstract:To determine the carrier frequency and pathogenic variants of common genetic disorders in the north Indian population by using next generation sequencing (NGS). Methods After pre-test counselling, 200 unrelated individuals (including 88 couples) were screened for pathogenic variants in 88 genes by NGS technology.
Profile of Pathogenic Mutations and Evaluation of Germline Genetic Testing Criteria in Consecutive Breast Cancer Patients Treated at a North Indian Tertiary Care Center
Abstract:The burden of hereditary breast cancer in India is not well defined. Moreover, genetic testing criteria (National Comprehensive Cancer Network [NCCN] and Mainstreaming Cancer Genetics [MCG] Plus) have never been validated in the Indian population.
Myoneuropathic presentation of limb girdle muscular dystrophy R8 with a novel TRIM32 mutation
Abstract:orted in fewer than 100 patients worldwide. Here, we report a male patient with progressive proximo-distal lower limb weakness with onset in the third decade who had mixed myopathic and neurogenic pattern in
HopA1 Effector from Pseudomonas syringae pv syringae Strain 61 Affects NMD Processes and Elicits Effector-Triggered Immunity
Abstract:Pseudomonas syringae-secreted HopA1 effectors are important determinants in host range expansion and increased pathogenicity. Their recent acquisitions via horizontal gene transfer in several non-pathogenic Pseudomonas strains worldwide have caused alarming increase in their virulence
Phenotypic expression and clinical outcomes in a South Asian PRKAG2 cardiomyopathy cohort
Abstract:The PRKAG2 syndrome is a rare autosomal dominant phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM), characterized by ventricular pre-excitation, progressive conduction system disease and left ventricular hypertrophy. This study describes the phenotype
Ophthatome™: an integrated knowledgebase of ophthalmic diseases for translating vision research into the clinic
Abstract:Medical big data analytics has revolutionized the human healthcare system by introducing processes that facilitate rationale clinical decision making, predictive or prognostic modelling of the disease progression and management, disease surveillance, overall impact on public health and research. Although, the electronic medical records (EMR) system is the digital
Infantile spasms: Etiology, lead time and treatment response in a resource limited setting.
Abstract:This study explores the etiology and lead time to treatment for infantile spasm (IS) patients and their effect on treatment responsiveness, in a limited resource setting. Patients with IS onset age ≤12 months', seen over 3 years were recruited retrospectively. Clinical information, neuroimaging and genetic results retrieved.
Seven novel genetic variants in a North Indian cohort with classical homocystinuria
Abstract:Classical homocystinuria is the most common cause of isolated homocystinuria. The variants of the CBS gene remain unidentified in Indian children with this disorder. Based on the hallmark clinical features, family history, and/or biochemical clues for classical homocystinuria
Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate
Abstract:Gallbladder cancer (GBC) is an aggressive gastrointestinal malignancy with no approved targeted therapy. Here, we analyze exomes (n = 160), transcriptomes (n = 115), and low pass whole genomes (n = 146) from 167 gallbladder cancers (GBCs) from patients in Korea, India and Chile.
A Case of Autosomal Dominant Ataxia with Vocal Cord Palsy Attributed to a Mutation in the PRNP Gene.
Abstract:Keywords: ataxia, CJD, familial, vocal cord palsy, autosomal dominant.
Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians
Abstract:Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population.
A Rare Neurological Presentation of Familial Hemophagocytic Lymphohistiocytosis.
Abstract:In this case report, we described a 15-year-old boy who presented with intermittent episodes of ataxia and diplopia since 6.5 years of age. Extensive workup done over several years was negative. Brain biopsy showed a neuroinflammatory disorder, and hence, differential diagnosis of chronic lymphocytic inflammation with pontine perivascular
Genetic analysis of familial hypercholesterolemia in Asian Indians: a single center study
Abstract:Familial Hypercholesterolemia (FH), an autosomal co-dominant disorder characterized by very high LDL cholesterol, is strongly associated with premature coronary artery disease. Molecular landscape of FH in Asian Indians is not well studied, although this ethnic group comprises a large proportion of the world population. Knowledge of mutations in these groups is useful for identifying persons affected with FH, saving their…
S100a4 upregulation in Pik3caH1047R;Trp53R270H;MMTV-Cre-driven mammary tumors promotes metastasis.
Abstract:PIK3CA mutations are frequent in human breast cancer. Pik3caH1047R mutant expression in mouse mammary gland promotes tumorigenesis. TP53 mutations co-occur with PIK3CA mutations in human breast cancers. We previously generated a conditionally activatable Pik3caH1047R;MMTV-Cre mouse model and found a few malignant sarcomatoid (spindle cell) carcinomas that had acquired spontaneous dominant-negative Trp53 mutations.
MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma
Abstract:Epidermal growth factor receptor (EGFR) targeted therapies have shown limited efficacy in head and neck squamous cell carcinoma (HNSCC) patients despite its overexpression. Identifying molecular mechanisms associated with acquired resistance to EGFR-TKIs such as erlotinib remains an unmet need and a therapeutic challenge.
Association of HLA-A, -B, DRB, and DQB Alleles with Persistent HPV-16 Infection in Women from Tamil Nadu, India
Abstract:Women with persistent human papillomavirus (HPV) infections have a high risk of developing cervical cancer (CaCx). HPV-16 alone accounts for more than 60% of CaCx worldwide. Most of the HPV infections are transient and only a subset of women develop persistent HPV-16 infection.
Prevalence of mutations in inherited retinal diseases: A comparison between the United States and India
Abstract:Studies evaluating next‐generation sequencing (NGS) for retinal disorders may not reflect clinical practice. We report results of retrospective analysis of patients referred for clinical testing at two institutions (US and India). Methods This retrospective study of 131 patients who underwent clinically
Prevalence of mutations in inherited retinal diseases: A comparison between the United States and India
Abstract:Studies evaluating next‐generation sequencing (NGS) for retinal disorders may not reflect clinical practice. We report results of retrospective analysis of patients referred for clinical testing at two institutions (US and India). Methods This retrospective study of 131 patients who underwent clinically validated targeted NGS or exome sequencing for a wide variety of clinical
Identification of African-Specific Admixture between Modern and Archaic Humans
Abstract:Recent work has demonstrated that two archaic human groups (Neanderthals and Denisovans) interbred with modern humans and contributed to the contemporary human gene pool. These findings relied on the availability of high-coverage genomes from both Neanderthals and Denisovans. Here we search for evidence of archaic admixture from a worldwide panel of 1,667 individuals using an approach that does not require…
The GenomeAsia 100K Project enables genetic discoveries across Asia
Abstract:The underrepresentation of non-Europeans in human genetic studies so far has limited the diversity of individuals in genomic datasets and led to reduced medical relevance for a large proportion of the world’s population. Population-specific reference genome datasets as well as genome-wide association studies in diverse populations are needed to address this issue.
A Computational Approach Identifies Immunogenic Features of Prognosis in Human Cancers.
Abstract:A large number of tumor intrinsic and extrinsic factors determine long-term survival in human cancers. In this study, we stratified 9120 tumors from 33 cancers with respect to their immune cell content and identified immunogenomic features associated with long-term survival.
Metabolite systems profiling identifies exploitable weaknesses in retinoblastoma.
Abstract:Retinoblastoma (RB) is a childhood eye cancer. Currently, chemotherapy, local therapy, and enucleation are the main ways in which these tumors are managed. The present work is the first study that uses constraint‐based reconstruction and analysis approaches to identify and explain RB‐specific survival strategies, which are RB tumor
Actionable Activating Oncogenic ERBB2/HER2 Transmembrane and Juxtamembrane Domain Mutations
Abstract:Deregulated HER2 is a target of many approved cancer drugs. We analyzed 111,176 patient tumors and identified recurrent mutations in HER2 transmembrane domain (TMD) and juxtamembrane domain (JMD) that include G660D, R678Q, E693K, and Q709L. Using a saturation mutagenesis screen and testing of patient-derived mutations we found several activating TMD and JMD mutations.
Is there a Chance to Promote Arteriogenesis by DPP4 Inhibitors Even in Type 2 Diabetes? A Critical Review.
Abstract:Cardiovascular diseases (CVD) are still the prevailing cause of death not only in industrialized countries, but even worldwide. Type 2 diabetes mellitus (type 2 DM) and hyperlipidemia, a metabolic disorder that is often associated with diabetes, are major risk factors for developing CVD. Recently, clinical trials proved the safety of gliptins in treating patients with type 2 DM.
A neoepitope derived from a novel human germline APC gene mutation in familial adenomatous polyposis shows selective immunogenicity
Abstract:Familial adenomatous polyposis (FAP) is an inherited condition arising from genetic defects in the Adenomatous polyposis coli (APC) gene. Carriers with mutations in the APC gene develop polyps in the colon and rectum which if not managed, transition into colon cancer. In this study, we identified a novel germline mutation in the APC gene in members of an FAP-affected (Familial…
Progressive nonparoxysmal chorea and dystonia due to myofibrillogenesis regulator-1 gene mutation
Abstract:Mutations in the myofibrillogenesis regulator gene (MR-1) causes paroxysmal non -kinesigenic dyskinesia (PNKD) characterized by episodic (paroxysmal) attacks of any combination of chorea, dystonia and athetosis ( MR-1/PNKD) [ 1 ]. This gene is transcribed into three alternatively spliced isoforms: long (MR-1L), medium (MR-1M) and small (MR-1S) [ 2 , 3 ].
A cancer vaccine approach for personalized treatment of Lynch Syndrome
Abstract:Snigdha Majumder, Rakshit Shah, Jisha Elias, Malini Manoharan, Priyanka Shah, Anjali Kumari, Papia Chakraborty, Vasumathi Kode, Yogesh Mistry, Karunakaran Coral, Bharti Mittal, Sakthivel Murugan SM, Lakshmi Mahadevan, Ravi Gupta, Amitabha Chaudhuri & Arati Khanna-Gupta. Lynch Syndrome (LS) is an inherited heterozygous
Identification of deletion-duplication in HEXA gene in five children with Tay-Sachs disease from India
Abstract:Background Tay-Sachs disease (TSD) is a sphingolipid storage disorder caused by mutations in the HEXA gene. To date, nearly 170 mutations of HEXA have been described, including only one 7.6 kb large deletion. Methods Multiplex Ligation-dependent Probe Amplification (MLPA) study was carried out in 5 unrelated patients for copy number
A novel splice variant in EMC1 is associated with cerebellar atrophy, visual impairment, psychomotor retardation with epilepsy
Abstract:Background Several genes have been implicated in a highly variable presentation of developmental delay with psychomotor retardation. Mutations in EMC1 gene have recently been reported. Herein, we describe a proband born of a consanguineous marriage, who presented with early infantile onset epilepsy, scaphocephaly, developmental delay, central hypotonia, muscle wasting, and severe cerebellar and brainstem atrophy.
Serum starvation of ARPE-19 changes the cellular distribution of cholesterol and Fibulin3 in patterns reminiscent of age-related macular degeneration
Abstract:Retinal pigment epithelium (RPE) has been implicated as key source of cholesterol-rich deposits at Bruch's membrane (BrM) and in drusen in aging human eye. We have shown that serum-deprivation of confluent RPE cells is associated with upregulation of cholesterol synthesis and accumulation of unesterified cholesterol (UC).
Asparagine Synthetase deficiency-report of a novel mutation and review of literature
Abstract:Asparagine synthetase deficiency is a rare inborn error of metabolism caused by a defect in ASNS, a gene encoding asparagine synthetase. It manifests with a severe neurological phenotype manifesting as severe developmental delay, congenital microcephaly, spasticity and refractory seizures. To date, nineteen patients from twelve unrelated families have been identified. Majority of the
Autosomal Recessive Spastic Ataxia of Charlevoix‐Saguenay (ARSACS)–First Report of Clinical and Imaging Features from India, and a Novel SACS Gene Duplication
Abstract:Autosomal recessive spastic ataxia of Charlevoix‐Saguenay (ARSACS) was described by Bouchard and colleagues in 1978 from Quebec, Canada, as a rare cause of autosomal recessive cerebellar ataxia. 1.2 Subsequent reports confirmed the presence of this condition in other parts of the world, including Europe and, in Asia, Japan.
Next-Generation Sequencing Reveals Novel Mutations in X-linked Intellectual Disability
Abstract:Robust diagnostics for many human genetic disorders are much needed in the pursuit of global personalized medicine. Next-generation sequencing now offers new promise for biomarker and diagnostic discovery, in developed as well as resource-limited countries. In this broader global health context, X-linked intellectual disability (XLID) is an inherited genetic disorder that is
Mycobacterium tuberculosis in Wild Asian Elephants, Southern India
Abstract:We tested 3 ild Asian elephants (Elephas maximus) in southern India and confirmed infection in 3 animals with Mycobacterium tuberculosis, an obligate human pathogen, by PCR and genetic sequencing. Our results indicate that tuberculosis may be spilling over from humans (reverse zoonosis) and emerging in wild elephants.
The utility and futility of targeted Next-generation sequencing for carrier detection in ‘At Risk’ couples
Abstract:Next generation sequencing has changed the approach to genetic diagnosis and testing in recent times. The days have arrived when a molecular genetic diagnosis can be attempted even without the availability of the proband or affected person. However this requires additional strong evidence of diagnosis in the proband, such as biochemical or radiological hallmarks. Needless to say, this attempt should…
Predicting Response to Immunosuppressive Therapy in Patients with Acquired Aplastic Anemia using EGFR and TWIST1 Expression Levels
Abstract:EGFR (epidermal growth factor receptor) is important for the proliferation of stem cells across the body including the hematopoietic niche. However, the role of EGFR in aplastic anemia and subsequent responses to standard-of-care therapy is unknown.TWIST is a basic helix-loop-helix transcription factor recently found to regulate the hematopoietic stem cell (HSC) niche.
Manitoba Oculotrichoanal Syndrome: First case report from India
Abstract:Manitoba-oculo-tricho-anal (MOTA) syndrome is very rare syndrome characterized by aberrant hairline, eye anomalies (ocular hypertelorism, cryptophthalmos, and upper eyelid colobomas), bifid nose, omphalocele and anorectal anomalies. MOTA syndrome was first reported in 1992 in Oji-cree community from the Island Lake region of Manitoba, Canada. Till date very few cases of MOTA have been reported and none from India.
A splice site mutation in HERC1 leads to Syndromic Intellectual Disability with macrocephaly and facial dysmorphism: Further delineation of the phenotypic spectrum
Abstract:We report on a sib pair of Indian origin presenting with intellectual disability, dysmorphism, and macrocephaly. Exome sequencing revealed a homozygous splice site HERC1 mutation in both probands. Functional analysis revealed use of an alternate splice site resulting in formation of a
The expression dynamics of mechanosensitive genes in extra-embryonic vasculature after heart starts to beat in chick embryo
Abstract:Fluid flow plays an important role in vascular development. However, the detailed mechanisms, particularly the link between flow and modulation of gene expression during vascular development, remain unexplored. In chick embryo, the key events of vascular development from initiation of heart beat to establishment of effective blood flow occur between the stages HH10 and HH13. Therefore, we propose a novel…
Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations
Abstract:We analyzed transcriptomes (n = 211), whole exomes (n = 99) and targeted exomes (n = 103) from 216 malignant pleural mesothelioma (MPM) tumors. Using RNA-seq data, we identified four distinct molecular subtypes: sarcomatoid, epithelioid, biphasic-epithelioid (biphasic-E) and biphasic-sarcomatoid (biphasic-S). Through exome analysis, we found BAP1, NF2, TP53, SETD2, DDX3X, ULK2, RYR2, CFAP45, SETDB1 and DDX51 to be significantly mutated…
A novel H395R mutation in MKKS/BBS6 causes retinitis pigmentosa and polydactyly without other findings of Bardet-Biedl or McKusick-Kaufman syndrome
Abstract:To identify the causative mutation in two siblings from a consanguineous family in India with retinitis pigmentosa (RP) and polydactyly without other findings of Bardet-Biedl syndrome (BBS). We also performed functional characterization of the mutant protein to explore its role in this limited form of BBS. Methods The siblings underwent a thorough ophthalmological examination, including retinal optical coherence tomography (OCT)…
First Report of Kufor‐Rakeb Syndrome (PARK 9) from India, and a Novel Nonsense Mutation in ATP13A2 Gene
Abstract:Kufor‐Rakeb syndrome (KRS; PARK 9) is a rare autosomal‐recessive form of juvenile‐onset Parkinson's disease (PD) caused by ATP13A2 gene mutations. The classical description of KRS is that of rapidly progressive symptoms in the form of parkinsonism, spasticity, supranuclear upgaze paresis, facial‐faucial‐finger minimyoclonus, visual hallucinations, oculogyric dystonic spasms, and
Identification of Novel Mutations in ABCA4 Gene: Clinical and Genetic Analysis of Indian Patients with Stargardt Disease.
Abstract:Stargardt disease (STGD) is the leading cause of juvenile macular degeneration associated with progressive central vision loss, photophobia, and colour vision abnormalities. In this study, we have described the clinical and genetic features of Stargardt patients from an Indian cohort.
Evolution of targeted therapies in cancer: opportunities and challenges in the clinic
Abstract:Targeted therapies have changed the course of cancer treatment in recent years. By reducing toxicity and improving outcome, these new generations of precision medicines have extended patient lives beyond what could be achieved by the use of nontargeted therapies. In the last 2 years, several new molecular entities targeting signaling proteins and immune pathways have gone through successful clinical development…
Cost-efficient HIV-1 drug resistance surveillance using multiplexed high-throughput amplicon sequencing: implications for use in low- and middle-income countries
Abstract:Increased trends of primary drug resistance mutations (DRMs) among treatment-naive HIV-1-infected patients in low- and middle-income countries (LMICs) and the non-availability of pre-antiretroviral therapy (ART) genotypic resistance testing (GRT) may severely affect future therapeutic outcomes. The main objective of this study was therefore to develop a simplified, cost- and labour-efficient but high-throughput GRT protocol to
Regulation of Macrophage Polarization by RON Receptor Tyrosine Kinase Signaling.
Abstract:The M1 and M2 states of macrophage polarization are the two extremes of a physiologic/phenotypic continuum that is dynamically influenced by environmental signals. The M1/M2 paradigm is an excellent framework to understand and appreciate some of the diverse functions that macrophages perform. Molecular analysis of mouse and human macrophages indicated that they gain M1 and M2-related functions after encountering specific…
Prevalence of genetic variants associated with cardiovascular disease risk and drug response in the Southern Indian population of Kerala
Abstract:This study reports the prevalence of five clinically significant variants associated with increased risk of cardiovascular disorders, and variable responses of individuals to commonly prescribed cardiovascular drugs in a South Indian population from the state of Kerala.
Recessive mutations in SLC38A8 cause Foveal Hypoplasia and Optic Nerve Misrouting without Albinism
Abstract:Foveal hypoplasia and optic nerve misrouting are developmental defects of the visual pathway and only co-occur in connection with albinism; to date, they have only been associated with defects in the melanin-biosynthesis pathway. Here, we report that these defects can occur independently of albinism in people with recessive mutations in the putative glutamine transporter gene SLC38A8.
Sequencing and analysis of a South Asian-Indian personal genome
Abstract:With over 1.3 billion people, India is estimated to contain three times more genetic diversity than Europe. Next-generation sequencing technologies have facilitated the understanding of diversity by enabling whole genome sequencing at greater speed and lower cost. While genomes from people of European and Asian descent have been sequenced, only recently has a single male genome from the