Browsing by Author "Panigrahi, Inusha"

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Clinical and Molecular Heterogeneity of Silver-Russell Syndrome and Therapeutic Challenges: A Systematic Review
(Bentham Science Publishers, 2022-03-16T00:00:00) Singh, Amit; Pajni, Ketan; Panigrahi, Inusha; Khetarpal, Preeti
Background: Silver-Russell syndrome (SRS) is a developmental disorder involving ex-treme growth failure, characteristic facial features and underlying genetic heterogeneity. As the clinical heterogeneity of SRS makes diagnosis a challenging task, the worldwide incidence of SRS could vary from 1:30,000 to 1:100,000. Although various chromosomal, genetic, and epigenetic mutations have been linked with SRS, the cause had only been identified in half of the cases. Material and Methods: To have a better understanding of the SRS clinical presentation and mutation/epimutation responsible for SRS, a systematic review of the literature was carried out using ap-propriate keywords in various scientific databases (PROSPERO protocol registration CRD42021273211). Clinical features of SRS have been compiled and presented corresponding to the specific genetic subtype. An attempt has been made to understand the recurrence risk and the role of model organisms in understanding the molecular mechanisms of SRS pathology, treatment, and management strategies of the affected patients through the analysis of selected literature. Results: 156 articles were selected to understand the clinical and molecular heterogeneity of SRS. Information about detailed clinical features was available for 228 patients only, and it was observed that body asymmetry and relative macrocephaly were most prevalent in cases with methylation defects of the 11p15 region. In about 38% of cases, methylation defects in ICRs or genomic mutations at the 11p15 region have been implicated. Maternal uniparental disomy of chromosome 7 (mUPD7) accounts for about 7% of SRS cases, and rarely, uniparental disomy of other autosomes (11, 14, 16, and 20 chromosomes) has been documented. Mutation in half of the cases is yet to be identified. Studies involving mice as experimental animals have been helpful in understanding the underlying molecular mechanism. As the clinical presentation of the syndrome varies a lot, treatment needs to be individualized with multidisciplinary effort. Conclusion: SRS is a clinically and genetically heterogeneous disorder, with most of the cases being implicated with a mutation in the 11p15 region and maternal disomy of chromosome 7. Recurrence risk varies according to the molecular subtype. Studies with mice as a model organism have been useful in understanding the underlying molecular mechanism leading to the characteristic clinical presentation of the syndrome. Management strategies often need to be individualized due to varied clinical presentations. � 2023 Bentham Science Publishers.
Components of IGF-axis in growth disorders: a systematic review and patent landscape report
(Springer, 2022-05-06T00:00:00) Singh, Amit; Pajni, Ketan; Panigrahi, Inusha; Dhoat, Navdeep; Senapati, Sabyasachi; Khetarpal, Preeti
Purpose: In this review, epi/genetic mutations of IGF-axis components associated with growth disorders have been summarized alongwith assessment of relevant diagnostic and therapeutic technology through patent literature. Methodology: PROSPERO protocol registration CRD42021279468. For scientific literature search Literature databases (PubMed, EMBASE, ScienceDirect, and Google Scholar) were queried using the appropriate syntax. Various filters were applied based on inclusion and exclusion criteria. Search results were further refined by two authors for finalizing studies to be included in this synthesis. For patent documents search Patent databases (Patentscope and Espacenet) were queried using keywords: IGF or IGFBP. Filters were applied according to International Patent Classification (IPC) and Cooperative Patent Classification (CPC). Search results were reviewed by two authors for inclusion in the patent landscape report. Results: For scientific literature analysis, out of 545 search results, 196 were selected for review based on the inclusion criteria. For Patent literature search, out of 485 results, 37 were selected for this synthesis. Conclusion: Dysregulation of IGF-axis components leads to various abnormalities and their key role in growth and development suggests epi/mutations or structural defects among IGF-axis genes can be associated with growth disorders and may explain some of the idiopathic short stature cases. Trend of patent filings indicate advent of recombinant technology for therapeutics. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Mutational Analysis in Gaucher Disease: Implications in Genetic Counseling and Management
(SciTechnol, 2016) Panigrahi, Inusha; Kalra, Jaswinder; Goyad, Prasoon; Khetarpal, Preeti; Munshi, Anjana
Gaucher disease (GD) is the most common LSD worldwide. The disease is caused due to mutations in β-glucocerobrosidase (GBA) gene located on chromosome 1. The mutations results in the deficient activity of acid β-glucosidase (glucocerebrosidase) enzyme. It is inherited in an autosomal recessive fashion and both men and women are affected equally. We report here two families wherein the mutation analysis for the disease was performed as the clinical features of the children were suggestive of GD. In the first family the enzyme analysis reports of the children were normal but GD was confirmed upon mutation analysis. In another family who had come for prenatal diagnosis, the parents were confirmed to be heterozygote of normal mutation whereas the foetus was found to be of carrier status. The family had already lost two children who had clinical features suggestive of Gaucher. We conclude that in some cases the enzyme analysis report may not be conclusive and mutation analysis has to be carried out to confirm the disorder. Prenatal diagnosis for lysosomal storage disorders like GD is also recommended among high risk couples.
Primordial dwarfism: overview of clinical and genetic aspects
(Springer Verlag, 2016) Khetarpal, Preeti; Das, Satrupa; Panigrahi, Inusha; Munshi, Anjana
Primordial dwarfism is a group of genetic disorders which include Seckel Syndrome, Silver?Russell Syndrome, Microcephalic Osteodysplastic Primordial Dwarfism types I/III, II and Meier?Gorlin Syndrome. This genetic disorder group is characterized by intra-uterine growth retardation and post-natal growth abnormalities which occur as a result of disorganized molecular and genomic changes in embryonic stage and, thus, it represents a unique area to study growth and developmental abnormalities. Lot of research has been carried out on different aspects; however, a consolidated review that discusses an overall spectrum of this disorder is not accessible. Recent research in this area points toward important molecular and cellular mechanisms in human body that regulate the complexity of growth process. Studies have emerged that have clearly associated with a number of abnormal chromosomal, genetic and epigenetic alterations that can predispose an embryo to develop PD-associated developmental defects. Finding and associating such fundamental changes to its subtypes will help in re-examination of alleged functions at both cellular and developmental levels and thus reveal the intrinsic mechanism that leads to a balanced growth. Although such findings have unraveled a subtle understanding of growth process, we further require active research in terms of identification of reliable biomarkers for different subtypes as an immediate requirement for clinical utilization. It is hoped that further study will advance the understanding of basic mechanisms regulating growth relevant to human health. Therefore, this review has been written with an aim to present an overview of chromosomal, molecular and epigenetic modifications reported to be associated with different subtypes of this heterogenous disorder. Further, latest findings with respect to clinical and molecular genetics research have been summarized to aid the medical fraternity in their clinical utility, for diagnosing disorders where there are overlapping physical attributes and simultaneously inform about the latest developments in PD biology. ? 2015, Springer-Verlag Berlin Heidelberg.
A systematic review of the monogenic causes of Non-Syndromic Hearing Loss (NSHL) and discussion of Current Diagnosis and Treatment options
(John Wiley and Sons Inc, 2022-09-12T00:00:00) Sharma, Nandita; Kumari, Divya; Panigrahi, Inusha; Khetarpal, Preeti
Hearing impairment is one of the most widespread inheritable sensory disorder affecting at least 1 in every 1000 born. About two-third of hereditary hearing loss (HHL) disorders are non-syndromic. To provide comprehensive update of monogenic causes of non-syndromic hearing loss (NSHL), literature search has been carried out with appropriate keywords in the following databases�PubMed, Google Scholar, Cochrane library, and Science Direct. Out of 2214 papers, 271 papers were shortlisted after applying inclusion and exclusion criterion. Data extracted from selected papers include information about gene name, identified pathogenic variants, ethnicity of the patient, age of onset, gender, title, authors' name, and year of publication. Overall, pathogenic variants in 98 different genes have been associated with NSHL. These genes have important role to play during early embryonic development in ear structure formation and hearing development. Here, we also review briefly the recent information about diagnosis and treatment approaches. Understanding pathogenic genetic variants are helpful in the management of affected and may offer targeted therapies in future. � 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.