Denys-Drash syndrome consists of the triad of progressive nephropathy characterised by diffuse
mesangial sclerosis (DMS), genital abnormalities, and Wilms tumour. Nephropathy may range
from early onset proteinuria to nephrotic syndrome to end stage renal failure. Genital malformations affects both external and internal genitalia. It may range from penoscrotal hypospadias,
bilateral cryptorchidism to an enlarged clitoris with fused labia and a urogenital sinus to atrophic
uterus to streak ovaries or dysgenetic testes. The risk of developing Wilms’ tumor may be as high
as 50%.
Bilateral Gonadblastoma and Dysgerminoma in an 18-Year-Old Female Patient wit...Crimsonpublishers-IGRWH
This case report describes a rare case of an 18-year-old female patient with 46XY, SRY gene mutation who was found to have bilateral gonadoblastoma and dysgerminoma during a planned prophylactic gonadectomy. Additional imaging found no signs of metastasis. After multidisciplinary consultation, an expectant management approach was chosen without additional surgery or chemotherapy given the controversial need for these treatments and the ability to effectively treat recurrence with chemotherapy. During 1.5 years of follow-up so far, there have been no signs of recurrence. This case contributes limited data on managing this rare type of germ cell tumor.
Genetic changes play an important role in the development of childhood tumors. There are three main categories of genes affected: proto-oncogenes, tumor suppressor genes, and DNA repair genes. Mutations in tumor suppressor genes like RB1 and TP53 can lead to cancers due to a loss of control of cell proliferation. Activation of proto-oncogenes also contributes to childhood cancers like leukemias and solid tumors. Molecular diagnostic techniques can identify genetic alterations that provide prognostic and therapeutic insights for managing childhood cancers.
DISEASES OF GENETIC MUTATION, TREATMENTS(2).pptxTasiumujahid
Genetic mutations can cause diseases by altering DNA sequences. There are two main types of genetic mutations - chromosomal mutations which change chromosome structure or number, and gene mutations which alter individual genes. Some diseases caused by genetic mutations include Klinefelter syndrome, hemophilia, fragile X syndrome, sickle cell anemia, Down syndrome, and cancer. The genetic basis for these diseases involves changes to genes, chromosomes, or DNA that disrupt normal cell functioning and development. Manifestations and treatment options vary depending on the specific disease.
Identification of a Novel Mutation (p.G328W) in the NR5A1 Gene in a Boy with ...CrimsonPublishersGJEM
This document summarizes a case report of a 46,XY newborn with ambiguous genitalia presenting with a novel mutation in the NR5A1 gene. The key points are:
- The newborn presented with micropenis, hypospadias, and bilateral inguinal gonads. Hormone testing showed a normal testosterone response to hCG.
- Genetic testing identified a novel heterozygous p.G328W mutation in the NR5A1 gene, which had not been previously reported. This mutation occurred de novo.
- The mutation affects a highly conserved residue in the ligand binding domain of SF1. While adrenal function was normal, the mutation is believed
This document provides an overview of current concepts in disorders of sexual development (DSD). It discusses the physiology of sex development and factors involved in testicular and ovarian differentiation. It describes the proposed classification system for DSDs put forth by consensus groups, which categorizes DSDs into three main groups: sex chromosome DSDs, 46,XY DSDs, and 46,XX DSDs. The document also discusses changes in nomenclature for DSDs from previous terms like "intersex" to the current umbrella term of DSD.
This document reports on a study of a homozygous PMS2 founder mutation, NM_000535.5:c.2002A>G, identified in Inuit families from Northern Quebec that displayed an attenuated cancer phenotype compared to typical constitutional mismatch repair deficiency (CMMRD). The mutation generates a de novo splice site that competes with the authentic site, resulting in reduced but detectable expression of full-length PMS2 protein in homozygotes. The median age at primary cancer diagnosis was 22 years in 13 individuals homozygous for the mutation, later than the typical age of 8 years for carriers of bi-allelic truncating PMS2 mutations. Residual expression of the full-length PMS2 transcript was
This study aims to investigate the functional relationship between the rs1111875 single nucleotide polymorphism (SNP) and type 2 diabetes susceptibility by determining the effect of the SNP on the expression of the HHEX and IDE genes. The study will generate isogenic beta cell lines that differ only in their rs1111875 genotype using CRISPR/Cas9 genome editing. Gene expression analysis will then be performed on the cell lines using TaqMan assays to measure relative expression of HHEX and IDE and determine if the risk allele of rs1111875 alters their expression levels, which could provide insight into how this SNP contributes to type 2 diabetes risk.
Bilateral Gonadblastoma and Dysgerminoma in an 18-Year-Old Female Patient wit...Crimsonpublishers-IGRWH
This case report describes a rare case of an 18-year-old female patient with 46XY, SRY gene mutation who was found to have bilateral gonadoblastoma and dysgerminoma during a planned prophylactic gonadectomy. Additional imaging found no signs of metastasis. After multidisciplinary consultation, an expectant management approach was chosen without additional surgery or chemotherapy given the controversial need for these treatments and the ability to effectively treat recurrence with chemotherapy. During 1.5 years of follow-up so far, there have been no signs of recurrence. This case contributes limited data on managing this rare type of germ cell tumor.
Genetic changes play an important role in the development of childhood tumors. There are three main categories of genes affected: proto-oncogenes, tumor suppressor genes, and DNA repair genes. Mutations in tumor suppressor genes like RB1 and TP53 can lead to cancers due to a loss of control of cell proliferation. Activation of proto-oncogenes also contributes to childhood cancers like leukemias and solid tumors. Molecular diagnostic techniques can identify genetic alterations that provide prognostic and therapeutic insights for managing childhood cancers.
DISEASES OF GENETIC MUTATION, TREATMENTS(2).pptxTasiumujahid
Genetic mutations can cause diseases by altering DNA sequences. There are two main types of genetic mutations - chromosomal mutations which change chromosome structure or number, and gene mutations which alter individual genes. Some diseases caused by genetic mutations include Klinefelter syndrome, hemophilia, fragile X syndrome, sickle cell anemia, Down syndrome, and cancer. The genetic basis for these diseases involves changes to genes, chromosomes, or DNA that disrupt normal cell functioning and development. Manifestations and treatment options vary depending on the specific disease.
Identification of a Novel Mutation (p.G328W) in the NR5A1 Gene in a Boy with ...CrimsonPublishersGJEM
This document summarizes a case report of a 46,XY newborn with ambiguous genitalia presenting with a novel mutation in the NR5A1 gene. The key points are:
- The newborn presented with micropenis, hypospadias, and bilateral inguinal gonads. Hormone testing showed a normal testosterone response to hCG.
- Genetic testing identified a novel heterozygous p.G328W mutation in the NR5A1 gene, which had not been previously reported. This mutation occurred de novo.
- The mutation affects a highly conserved residue in the ligand binding domain of SF1. While adrenal function was normal, the mutation is believed
This document provides an overview of current concepts in disorders of sexual development (DSD). It discusses the physiology of sex development and factors involved in testicular and ovarian differentiation. It describes the proposed classification system for DSDs put forth by consensus groups, which categorizes DSDs into three main groups: sex chromosome DSDs, 46,XY DSDs, and 46,XX DSDs. The document also discusses changes in nomenclature for DSDs from previous terms like "intersex" to the current umbrella term of DSD.
This document reports on a study of a homozygous PMS2 founder mutation, NM_000535.5:c.2002A>G, identified in Inuit families from Northern Quebec that displayed an attenuated cancer phenotype compared to typical constitutional mismatch repair deficiency (CMMRD). The mutation generates a de novo splice site that competes with the authentic site, resulting in reduced but detectable expression of full-length PMS2 protein in homozygotes. The median age at primary cancer diagnosis was 22 years in 13 individuals homozygous for the mutation, later than the typical age of 8 years for carriers of bi-allelic truncating PMS2 mutations. Residual expression of the full-length PMS2 transcript was
This study aims to investigate the functional relationship between the rs1111875 single nucleotide polymorphism (SNP) and type 2 diabetes susceptibility by determining the effect of the SNP on the expression of the HHEX and IDE genes. The study will generate isogenic beta cell lines that differ only in their rs1111875 genotype using CRISPR/Cas9 genome editing. Gene expression analysis will then be performed on the cell lines using TaqMan assays to measure relative expression of HHEX and IDE and determine if the risk allele of rs1111875 alters their expression levels, which could provide insight into how this SNP contributes to type 2 diabetes risk.
Human genetic variation can influence treatment prognosis for hepatitis C virus (HCV). A single nucleotide polymorphism near the IFNL3 gene indicates natural resistance to type 1 HCV, with the T variant associated with poorer treatment outcomes. Additionally, a polymorphism in the interleukin-23 receptor gene correlates with reduced risk of HCV-related liver cancer. HCV appears to have evolved to benefit from allelic variations between geographic regions. Future treatment may focus on precise virus-genome interactions. Mapping the entire human genome could increase understanding of connections between HCV and its human host.
This study sequenced four genes (TNNT3, TNNI2, TPM2, MYH3) in 19 individuals with distal arthrogryposis (DA) to search for pathogenic mutations. No mutations were found in the sequenced regions for the 13 individuals with unclassified DA or 5 with Sheldon-Hall syndrome. A previously reported pathogenic mutation in MYH3 was identified in the single individual with Freeman-Sheldon syndrome, providing further evidence that mutations in this gene cause this condition. The results suggest that mutations in other regions of the genes or in non-coding regions may be responsible for the unclassified DA cases.
The document discusses using targeted next-generation sequencing (NGS) panels to identify genetic causes of nephrotic diseases in individuals with unknown etiology. The study found rare pathogenic/likely pathogenic mutations in nephrotic disease-related genes in 12% of patients using the ACMG-AMP variant classification standards. NGS can improve diagnosis accuracy for nephrotic diseases by discovering uncommon pathogenic variations compatible with clinical diagnoses in 65% of samples. The document provides background on genetics, genetic variations, inheritance patterns, and NGS techniques for detecting mutations.
The study analyzed 259 patients with craniosynostosis for mutations in FGFR2. While most mutations were found in exons IIIa and IIIc, the hotspot regions previously identified, the study uncovered mutations in seven additional exons of FGFR2. This included six distinct mutations in the tyrosine kinase domain and one in the IgII domain. The majority of patients with atypical mutations were diagnosed with Pfeiffer or Crouzon syndrome. Overall, FGFR2 mutations were identified in 9.8% of patients in the prospectively ascertained sample. The spectrum of FGFR2 mutations causing craniosynostosis is wider than previously recognized, but exons IIIa and IIIc remain a major hotspot.
Klinefelter syndrome is caused by the presence of at least one extra X chromosome in males, resulting in a 47,XXY karyotype. It is one of the most common sex chromosome aneuploidies, occurring in around 1 in 500-1000 live male births. Individuals with Klinefelter syndrome exhibit physical traits such as tall stature, small testes, gynecomastia, and cognitive/behavioral issues. Diagnosis can be made through karyotype analysis of cells showing the extra X chromosome. Treatment involves testosterone therapy to promote secondary sex characteristics, though it does not treat infertility issues associated with the condition.
This document discusses Wilms tumor, a type of kidney cancer that typically affects children. It covers the epidemiology, biology, genetics, pathology, screening, evaluation, staging and treatment of Wilms tumor. Key points include that Wilms tumor is the most common malignant renal tumor in children, occurring most often in children under 5 years old. Genetic syndromes like WAGR and Beckwith-Wiedemann syndrome are associated with an increased risk. Pathology and staging help determine prognosis and guide treatment, which typically involves surgery and chemotherapy. Close screening is important due to the risk of bilateral tumors.
Whole exome sequencing was performed on a cohort of patients with DOORS syndrome to identify the genetic basis. Homozygous or compound heterozygous mutations in the TBC1D24 gene were identified in several patients. Further analysis showed that the mutations cause loss of function of the TBC1D24 protein, implicating defective vesicular trafficking as the potential cause of DOORS syndrome. However, further studies are still needed to fully understand the role of TBC1D24 and the genetic heterogeneity of this rare disorder.
Epigenetics and cell fate in JIA and pulmonary fibrosis by Jim HagoodSystemic JIA Foundation
This document discusses the potential role of epigenetic mechanisms in idiopathic pulmonary fibrosis (IPF) and juvenile idiopathic arthritis (JIA). It outlines how epigenetic changes like DNA methylation and histone modifications can alter gene expression and cell phenotypes, contributing to diseases like IPF that involve remodeling of lung tissue. Studies have found differential methylation and expression of genes in IPF lung tissue. Epigenetic therapies targeting mechanisms like DNA methylation and histone acetylation may one day help treat IPF and other diseases. The document also discusses how epigenetics may contribute to autoimmunity and JIA, noting differences in T cell methylation profiles between JIA patients and controls.
Mutations in DNA can lead to diseases like cancer. DNA is made up of genes that contain coded messages telling cells how to behave. Mutation of DNA signals can cause cells to replicate excessively and mutate, forming tumors and cancer. There are different types of mutations, such as missense mutations where one DNA nucleotide is replaced, changing the amino acid specified. Gene mutations occur regularly in cells, but tumor suppressor proteins normally eliminate damaged cells to prevent cancer. Inherited mutations in certain genes increase cancer risk.
This document summarizes research on the role of NFAT5 deficiency in immunodeficiency and autoimmune enterocolopathy. The researchers identified a deletion of the NFAT5 gene in a patient with unexplained infections and chronic intestinal inflammation. Further analysis showed NFAT5 deficiency resulted in reduced natural killer cells and impaired T cell function and cytokine production. Studies in human cells and mouse models confirmed the link between immune cell dysfunction and NFAT5 deficiency. The research demonstrates how genetic analysis can help clinical diagnosis and provide novel insights into disease mechanisms.
This document presents a study plan to investigate molecular markers and toll-like receptor expression in myelodysplastic syndrome (MDS) patients in Assam, India. The study aims to measure mutation levels of genes like TET2, SAXL1, RUNX1, RAS, and TP53 in MDS patients and determine expression of toll-like receptors TLR1-10 at mRNA and protein levels. The methodology involves collecting blood samples from MDS patients, extracting RNA and protein, and using techniques like qRT-PCR, ELISA, western blotting, and flow cytometry for analysis. The expected significance is that the study may help explore gene expression and mutation patterns in MDS patients in Assam and support approaches for treating
Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell...semualkaira
anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy
Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell...semualkaira
anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy. Several studies reported a sex disparity
in ASCC prognosis showing a better survival for female compared
to men. Methods: we examined 1,380 patients with ASCC who received comprehensive genomic profiling as part of routine clinical
care and present key
This presentation on Epigenetics is most advanced and evidence based one. Its Very helpful for Genetics students and research fellows, Reproductive Medicine specialist, Reproductive Biologist, Infertility practitioners
Managment Of Long Term Care In Era Covid-19komalicarol
COVID-19 gives the chance to address long-term care categories
that are sometimes disregarded and undervalued, such as nursing
and residential homes, as well as homecare. Each method of delivering long-term care must meet the highest possible standards
of ongoing care and quality of life. More study and evaluation are
needed to aid decision-making and policy-making, particularly on
the cost-effectiveness and cost-quality elements for each country,
region, or system.
Renal failure and Quality ofLlife Indicators in Kidney Transplantationkomalicarol
This article discusses quality of life indicators for patients undergoing kidney transplantation. It reviews several tools used to measure quality of life, including the SF-36, EQ-5D, and KDQOL questionnaires. Overall quality of life is generally improved after a successful kidney transplant compared to dialysis. However, factors like side effects of immunosuppressive drugs and the risk of rejection can still impact quality of life. The article concludes that while transplantation is associated with lower mortality and better quality of life than long-term dialysis, certain patient and treatment factors must be considered when evaluating individual quality of life outcomes.
A case of childhood Burkitt's lymphoma with gingival swelling as the first sy...komalicarol
This case report describes a 4-year-old child who presented with gingival swelling as the initial symptom of Burkitt's lymphoma. The child was eventually diagnosed with stage IV Burkitt's lymphoma/leukemia based on bone marrow and genetic testing. After initial chemotherapy, the gingival swelling and right cheek swelling recurred, indicating disease recurrence. The child received further chemotherapy but ultimately passed away half a year later. This case highlights that gingival swelling can be an early oral symptom of systemic disease like Burkitt's lymphoma. Dentists and oral physicians play an important role in identifying signs of systemic conditions through oral examinations.
Neuropsychiatric Profiles of Brivaracetam: A Literature Reviewkomalicarol
Anti-seizure medications (ASMs) can cause cognitive or behavioral adverse drug reactions, which is a significant consideration
when selecting an appropriate ASM. Brivaracetam (BRV) is a
newer synaptic vesicle protein 2A ligand, which is expected to
have less neuropsychiatric adverse effects due to its mechanism of
action. To understand the impact of BRV on cognition and behavior compared with other ASMs, we conducted literatures searching
from PubMed and MEDLINE databases. After the screening process, a total of two animal studies, one randomized controlled trial, one pooled-analysis of clinical trials, one controlled study and
nine observational studies were included. Animal studies showed
that BRV did not worsen cognition or behavior performance in rodents. Human studies showed that BRV had less cognitive adverse
events compared with other second or third generation ASMs. In
addition, currently available evidence suggests that behavioral disturbance is less common with BRV compared with levetiracetam.
This review revealed that BRV has a limited impact on cognition
and behavior. For patients who are intolerant to levetiracetam
and have levetiracetam-related behavioral side effects, switching
to BRV could be beneficial. However, the heterogeneity between
studies makes the quality of the evidence weak and further trials
are needed to confirm the findings.
Clinical and evolutionary features of SARS CoV-2 infection (COVID-19) in chil...komalicarol
Starting with December 2019 the medical world has faced a
new challenge as a consequence of a new type of coronavirus-2019-nCoV, similar to several familiar strains that determine
a comparable symptomatology (SARS- severe acute respiratory syndrome, MERS- Middle East severe acute respiratory syndrome), subsequently named SARS CoV-2, while the disease it
causes- COVID-19. The virus is of animal origin and through an
intermediate host (probably also a mammal) it suffered genetic
changes thus acquiring human cells receptors. In consequence,
SARS CoV-2 virus affects both children and even more frequently where it determines more severe clinical forms of disease. In
children, COVID-19 has various clinical forms, from asymptomatic ones to severe ones, complicated by multisystem inflammatory
syndrome (MIS-C Multisystem Inflammatory Syndrome – Child
or PIMS - TS (Paediatric Multisystem Inflammatory Syndrome
temporally associated with COVID-19) that sometimes can lead
to death
Viral load and antibody responses in an asymptomatic/minimally symptomatic SA...komalicarol
Asymptomatic patients with severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), are silent carriers of the disease. We
aimed to characterize their dynamics of disease occurrence, viral
shedding and antibody responses using a cohort of asymptomatic/
minimally symptomatic patients from Sri Lanka during the first
wave of COVID-19.
Vonlay; A paradigm shift in post endodontic restoration: A case report.komalicarol
Porcelain veneers have long been a popular restorative option that
have evolved into a well- accepted treatment that can be fabricated
in various ways. Onlays are another common treatment modality
used in contemporary dentistry to restore large areas of decay and
to replace old restorations. With the availability of newer highstrength materials such as lithium disilicate and processing technologies like CAD/CAM and heat pressing, dental professionals
are now able to produce highly esthetic, high-strength restorations
that blend seamlessly with the natural dentition while also withstanding posterior occlusal forces. A tooth more complex restoration is required after endodontic treatment when compared to normal tooth restoration, because of factors such as extensive caries,
post-treatment root canal dentin and even the economics condition
of the patient.One such design proposed by Dr.Ronald E Goldstein
is “Veenerlay”or “Vonlay”. Vonlay is a blend of an onlay with an
extended buccal veneer surface for use in premolar region, where
there is sufficient enamel present to bond. This restorative option
requires a much less invasive preparation than a full coverage
crown but provides the same structural benefits. Thus, the aim of
this case report is to present a case of Vonlay following endodontic
treatement of lower mandibular premol
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Human genetic variation can influence treatment prognosis for hepatitis C virus (HCV). A single nucleotide polymorphism near the IFNL3 gene indicates natural resistance to type 1 HCV, with the T variant associated with poorer treatment outcomes. Additionally, a polymorphism in the interleukin-23 receptor gene correlates with reduced risk of HCV-related liver cancer. HCV appears to have evolved to benefit from allelic variations between geographic regions. Future treatment may focus on precise virus-genome interactions. Mapping the entire human genome could increase understanding of connections between HCV and its human host.
This study sequenced four genes (TNNT3, TNNI2, TPM2, MYH3) in 19 individuals with distal arthrogryposis (DA) to search for pathogenic mutations. No mutations were found in the sequenced regions for the 13 individuals with unclassified DA or 5 with Sheldon-Hall syndrome. A previously reported pathogenic mutation in MYH3 was identified in the single individual with Freeman-Sheldon syndrome, providing further evidence that mutations in this gene cause this condition. The results suggest that mutations in other regions of the genes or in non-coding regions may be responsible for the unclassified DA cases.
The document discusses using targeted next-generation sequencing (NGS) panels to identify genetic causes of nephrotic diseases in individuals with unknown etiology. The study found rare pathogenic/likely pathogenic mutations in nephrotic disease-related genes in 12% of patients using the ACMG-AMP variant classification standards. NGS can improve diagnosis accuracy for nephrotic diseases by discovering uncommon pathogenic variations compatible with clinical diagnoses in 65% of samples. The document provides background on genetics, genetic variations, inheritance patterns, and NGS techniques for detecting mutations.
The study analyzed 259 patients with craniosynostosis for mutations in FGFR2. While most mutations were found in exons IIIa and IIIc, the hotspot regions previously identified, the study uncovered mutations in seven additional exons of FGFR2. This included six distinct mutations in the tyrosine kinase domain and one in the IgII domain. The majority of patients with atypical mutations were diagnosed with Pfeiffer or Crouzon syndrome. Overall, FGFR2 mutations were identified in 9.8% of patients in the prospectively ascertained sample. The spectrum of FGFR2 mutations causing craniosynostosis is wider than previously recognized, but exons IIIa and IIIc remain a major hotspot.
Klinefelter syndrome is caused by the presence of at least one extra X chromosome in males, resulting in a 47,XXY karyotype. It is one of the most common sex chromosome aneuploidies, occurring in around 1 in 500-1000 live male births. Individuals with Klinefelter syndrome exhibit physical traits such as tall stature, small testes, gynecomastia, and cognitive/behavioral issues. Diagnosis can be made through karyotype analysis of cells showing the extra X chromosome. Treatment involves testosterone therapy to promote secondary sex characteristics, though it does not treat infertility issues associated with the condition.
This document discusses Wilms tumor, a type of kidney cancer that typically affects children. It covers the epidemiology, biology, genetics, pathology, screening, evaluation, staging and treatment of Wilms tumor. Key points include that Wilms tumor is the most common malignant renal tumor in children, occurring most often in children under 5 years old. Genetic syndromes like WAGR and Beckwith-Wiedemann syndrome are associated with an increased risk. Pathology and staging help determine prognosis and guide treatment, which typically involves surgery and chemotherapy. Close screening is important due to the risk of bilateral tumors.
Whole exome sequencing was performed on a cohort of patients with DOORS syndrome to identify the genetic basis. Homozygous or compound heterozygous mutations in the TBC1D24 gene were identified in several patients. Further analysis showed that the mutations cause loss of function of the TBC1D24 protein, implicating defective vesicular trafficking as the potential cause of DOORS syndrome. However, further studies are still needed to fully understand the role of TBC1D24 and the genetic heterogeneity of this rare disorder.
Epigenetics and cell fate in JIA and pulmonary fibrosis by Jim HagoodSystemic JIA Foundation
This document discusses the potential role of epigenetic mechanisms in idiopathic pulmonary fibrosis (IPF) and juvenile idiopathic arthritis (JIA). It outlines how epigenetic changes like DNA methylation and histone modifications can alter gene expression and cell phenotypes, contributing to diseases like IPF that involve remodeling of lung tissue. Studies have found differential methylation and expression of genes in IPF lung tissue. Epigenetic therapies targeting mechanisms like DNA methylation and histone acetylation may one day help treat IPF and other diseases. The document also discusses how epigenetics may contribute to autoimmunity and JIA, noting differences in T cell methylation profiles between JIA patients and controls.
Mutations in DNA can lead to diseases like cancer. DNA is made up of genes that contain coded messages telling cells how to behave. Mutation of DNA signals can cause cells to replicate excessively and mutate, forming tumors and cancer. There are different types of mutations, such as missense mutations where one DNA nucleotide is replaced, changing the amino acid specified. Gene mutations occur regularly in cells, but tumor suppressor proteins normally eliminate damaged cells to prevent cancer. Inherited mutations in certain genes increase cancer risk.
This document summarizes research on the role of NFAT5 deficiency in immunodeficiency and autoimmune enterocolopathy. The researchers identified a deletion of the NFAT5 gene in a patient with unexplained infections and chronic intestinal inflammation. Further analysis showed NFAT5 deficiency resulted in reduced natural killer cells and impaired T cell function and cytokine production. Studies in human cells and mouse models confirmed the link between immune cell dysfunction and NFAT5 deficiency. The research demonstrates how genetic analysis can help clinical diagnosis and provide novel insights into disease mechanisms.
This document presents a study plan to investigate molecular markers and toll-like receptor expression in myelodysplastic syndrome (MDS) patients in Assam, India. The study aims to measure mutation levels of genes like TET2, SAXL1, RUNX1, RAS, and TP53 in MDS patients and determine expression of toll-like receptors TLR1-10 at mRNA and protein levels. The methodology involves collecting blood samples from MDS patients, extracting RNA and protein, and using techniques like qRT-PCR, ELISA, western blotting, and flow cytometry for analysis. The expected significance is that the study may help explore gene expression and mutation patterns in MDS patients in Assam and support approaches for treating
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anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy. Several studies reported a sex disparity
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COVID-19 gives the chance to address long-term care categories
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and residential homes, as well as homecare. Each method of delivering long-term care must meet the highest possible standards
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the cost-effectiveness and cost-quality elements for each country,
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This case report describes a 4-year-old child who presented with gingival swelling as the initial symptom of Burkitt's lymphoma. The child was eventually diagnosed with stage IV Burkitt's lymphoma/leukemia based on bone marrow and genetic testing. After initial chemotherapy, the gingival swelling and right cheek swelling recurred, indicating disease recurrence. The child received further chemotherapy but ultimately passed away half a year later. This case highlights that gingival swelling can be an early oral symptom of systemic disease like Burkitt's lymphoma. Dentists and oral physicians play an important role in identifying signs of systemic conditions through oral examinations.
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Anti-seizure medications (ASMs) can cause cognitive or behavioral adverse drug reactions, which is a significant consideration
when selecting an appropriate ASM. Brivaracetam (BRV) is a
newer synaptic vesicle protein 2A ligand, which is expected to
have less neuropsychiatric adverse effects due to its mechanism of
action. To understand the impact of BRV on cognition and behavior compared with other ASMs, we conducted literatures searching
from PubMed and MEDLINE databases. After the screening process, a total of two animal studies, one randomized controlled trial, one pooled-analysis of clinical trials, one controlled study and
nine observational studies were included. Animal studies showed
that BRV did not worsen cognition or behavior performance in rodents. Human studies showed that BRV had less cognitive adverse
events compared with other second or third generation ASMs. In
addition, currently available evidence suggests that behavioral disturbance is less common with BRV compared with levetiracetam.
This review revealed that BRV has a limited impact on cognition
and behavior. For patients who are intolerant to levetiracetam
and have levetiracetam-related behavioral side effects, switching
to BRV could be beneficial. However, the heterogeneity between
studies makes the quality of the evidence weak and further trials
are needed to confirm the findings.
Clinical and evolutionary features of SARS CoV-2 infection (COVID-19) in chil...komalicarol
Starting with December 2019 the medical world has faced a
new challenge as a consequence of a new type of coronavirus-2019-nCoV, similar to several familiar strains that determine
a comparable symptomatology (SARS- severe acute respiratory syndrome, MERS- Middle East severe acute respiratory syndrome), subsequently named SARS CoV-2, while the disease it
causes- COVID-19. The virus is of animal origin and through an
intermediate host (probably also a mammal) it suffered genetic
changes thus acquiring human cells receptors. In consequence,
SARS CoV-2 virus affects both children and even more frequently where it determines more severe clinical forms of disease. In
children, COVID-19 has various clinical forms, from asymptomatic ones to severe ones, complicated by multisystem inflammatory
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minimally symptomatic patients from Sri Lanka during the first
wave of COVID-19.
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Porcelain veneers have long been a popular restorative option that
have evolved into a well- accepted treatment that can be fabricated
in various ways. Onlays are another common treatment modality
used in contemporary dentistry to restore large areas of decay and
to replace old restorations. With the availability of newer highstrength materials such as lithium disilicate and processing technologies like CAD/CAM and heat pressing, dental professionals
are now able to produce highly esthetic, high-strength restorations
that blend seamlessly with the natural dentition while also withstanding posterior occlusal forces. A tooth more complex restoration is required after endodontic treatment when compared to normal tooth restoration, because of factors such as extensive caries,
post-treatment root canal dentin and even the economics condition
of the patient.One such design proposed by Dr.Ronald E Goldstein
is “Veenerlay”or “Vonlay”. Vonlay is a blend of an onlay with an
extended buccal veneer surface for use in premolar region, where
there is sufficient enamel present to bond. This restorative option
requires a much less invasive preparation than a full coverage
crown but provides the same structural benefits. Thus, the aim of
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athletes and the elderly leading to falls. Cases are individual and
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patient with a remarkable snakelike dilatation of the right coronary
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Growth Charts-Curves of Children's Height - How to Construct Themkomalicarol
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to their 17 or 20 years old instantaneously. It takes a long-capricious time of mental and physical activities to grow. As regards
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Those in their late adolescence in 2007 were not the beneficiaries
of free milk, when they were in primary school.
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discussed in order to outline a comprehensive model that considered the differences between the parties involved, as well as their
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CLASSIFICATION OF H1 ANTIHISTAMINICS-
FIRST GENERATION ANTIHISTAMINICS-
1)HIGHLY SEDATIVE-DIPHENHYDRAMINE,DIMENHYDRINATE,PROMETHAZINE,HYDROXYZINE 2)MODERATELY SEDATIVE- PHENARIMINE,CYPROHEPTADINE, MECLIZINE,CINNARIZINE
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AZELASTINE,MIZOLASTINE,EBASTINE,RUPATADINE. Mechanism of action of 2nd generation antihistaminics-
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4) Anticholinergic action- many H1 blockers
in addition antagonize muscarinic actions of ACh. BUT IN 2ND gen histaminics there is Higher H1 selectivitiy : no anticholinergic side effects
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because the population to be treated is known to include substantial numbers of
geriatric patients (e.g., hypertension).
Fexofenadine is sold under the brand name Allegra.
It is a selective peripheral H1 blocker. It is classified as a second-generation antihistamine because it is less able to pass the blood–brain barrier and causes lesser sedation, as compared to first-generation antihistamines.
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2. **Dermis**: Located beneath the epidermis, the dermis contains connective tissue, blood vessels, hair follicles, and sweat glands. It plays a vital role in supporting and nourishing the epidermis, regulating body temperature, and housing sensory receptors for touch, pressure, temperature, and pain.
3. **Hypodermis**: Also known as the subcutaneous layer, it consists of fat and connective tissue that anchors the skin to underlying structures like muscles and bones. It provides insulation, cushioning, and energy storage.
Skin performs essential functions such as regulating body temperature through sweat production and blood flow control, synthesizing vitamin D when exposed to sunlight, and serving as a sensory interface with the external environment.
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1. Prenatal Diagnosis of Denys-Drash Syndrome
Ashutosh G1*
, Gupta GG2
, Annu Y2
, Kumar JA3
, Syed FT4 and Pankaj S4
1
Department of Fetal Medicine & Clinical Geneticist, Max Super Speciality Hospital, India
2
Department of Obgyn, Max Super Speciality Hospital, India
3
Department of Radiology, T S M Hospital and Medical college, India
4
Department of Radiology, Artemis Health Institute, India
Volume 1 Issue 1- 2018
Received Date: 20 June 2018
Accepted Date: 10 July 2018
Published Date: 17 July 2018
1. Abstract
Denys-Drash syndrome consists of the triad of progressive nephropathy characterised by diffuse
mesangial sclerosis (DMS), genital abnormalities, and Wilms tumour. Nephropathy may range
from early onset proteinuria to nephrotic syndrome to end stage renal failure. Genital malforma-
tions affects both external and internal genitalia. It may range from penoscrotal hypospadias,
bilateral cryptorchidism to an enlarged clitoris with fused labia and a urogenital sinus to atrophic
uterus to streak ovaries or dysgenetic testes. The risk of developing Wilms’ tumor may be as high
as 50%.
A primigravida with screen positive for trisomy 21 was evaluated for further work up. Antenatal
ultrasound showed oligohydramnios with failure of growth. Both foetal kidneys were visualized
with normal echogenicity; with suspicion of genital ambiguity. Antenatal case with suspected
ambiguous genitalia, oligohydramnios and failure of growth; amniocentesis was done and chro-
mosomal microarray analysis (CMA) was done. It identified a micro deletion of 20 kilo base
pairs (Kbp) in WT1 gene located at 11p13 including both exonic and intronic regions. Advantage
of chromosomal micro array is higher resolution which helps in identifying additional clinical
significant abnormality.
Annals of Clinical and Medical
Case Reports
Citation: Ashutosh G, Gupta GG, Annu Y, Kumar JA, Syed FT and Pankaj S. Prenatal Diagnosis of Denys-
Drash Syndrome. Annals of Clinical and Medical Case Reports. 2018; 1(1): 1-5
United Prime Publications: http://unitedprimepub.com
*Corresponding Author (s): Gupta Ashutosh, Department of Fetal Medicine & Clinical
Geneticist, Max Super Speciality Hospital, India, E-mail: dr_ashutosh75@rediffmail.com
Case Presentation
3. Prenatal Diagnosis of Denys-Drash Syndrome
In 1967, Denys et al. described the triad of ambiguous genitalia,
nephrotic syndrome and Wilms’ tumor in an XX/ XY mosaic [1].
Drash et al. [2] described this triad in two patients and suggested
that it may be a syndrome [2].
4. Case Presentation
31 years old primigravida with quadruple test report screen
positive for trisomy 21 as 1:181 was being referred to the foetal
medicine department for further work up. Antenatal ultrasound
showed oligohydramnios (amniotic fluid index – 8.0 cm) with
failure of growth (Figure 1).
2. Key words
Triad; Nephropathy; Microarray;
Ambiguous; Genitalia; Failure;
Micro deletion; CMA, WT1
Figure 1: Antenatal transabdominal ultrasound showing bilateral renal tissues
with respective renal pelvis.
3. deletion; 3 of the 5 had a frame shift or missense mutation in
exon 7, 9 or 10 in the remaining allele.
WT1 is located on chromosome 11p13, it encodes zinc finger
domains and its product plays a key role in the regulation of gene
transcription [4]. Expression of WT1 is observed in the glo-
merular epithelium of the kidneys and the genital ridge during
the embryonic period, thus WT1 is thought to have a functional
role in renal and gonadal organogenesis [5]. The WT1 tumour
suppressor gene encodes a transcriptional factor containing
four zinc fingers. [6,7] WT1 gene has two alternative splicing re-
gions, one consisting of 17 amino acids which are encoded by
the whole of exon 5 and the other comprising three amino acids
(lysine, threonine, and serine (KTS)) situated between the third
and fourth zinc fingers encoded by the 3’ end of exon 9. Four
isoforms of the gene thus occur depending on the presence or
absence of these regions [8].
These isoforms are present in a fixed proportion in tissues where
they are expressed. WT1 is expressed from the condensing mes-
enchyme to mature podocytes in fetal kidneys, genital ridges and
fetal gonads. Therefore, this gene is thought to play an important
role in the development of the kidneys and gonads [9,10].
This intron 9 mutation leads to impairment of exon9 alterna-
tive splicing with a consequent decrease in the +KTS isoform,
thereby resulting in a quantitative +KTS/−KTS isoform imbal-
ance. Depending on exonic or intronic mutations, clinical fea-
tures vary amongst the patients.
Exonic mutations clinically had either Denys-Drash syndrome
or IDMS. WT1 mutations were missense mutations within the
second or the third zinc finger encoded by exon 8 or 9, respec-
tively. Intron 9 splicing donor site mutations, the clinical features
are consistent with Frasier syndrome.
These isoforms have different DNA binding properties [11]; the −
KTS isoform has greater binding affinity for growth related genes
[12]. Two of these isoforms have been shown to vary in subnu-
clear localisation. The +KTS isoform appears to be involved in
post-transcriptional RNA processing in association with splicing
factors, while the −KTS isoform is situated in the transcriptional
factor domain [13,14].
Denys-Drash syndrome (DDS) is characterised by WT1 muta-
tions, early onset renal failure, abnormal sex differentiation and a
predisposition to Wilms tumour [1,2]. WT1mutations have mis-
sense changes in exon 8 or 9 affecting zinc finger 2 or 3. Germline
mutations in WT1 have been reported in the majority of DDS
patients [15,16] Missense point mutations in exon 7 are very rare
[15].
Usually, WT1 missense mutations are detected in exons 8 or 9
and affect zinc fingers 2 or 3, which show a high level of homol-
ogy to the three zinc fingers of EGR1 and are believed to be im-
portant for their binding capacity to WT1 DNA targets [17].
Functional impairment of this gene is considered to give rise to
urogenital abnormalities and Wilms tumours. Denys-Drash syn-
drome and Frasier syndrome, both of which are characterised by
nephropathy with genital abnormalities
Denys-Drash syndrome consists of the triad of progressive ne-
phropathy characterised by diffuse mesangial sclerosis (DMS),
genital abnormalities, and Wilms tumour [18]. The incomplete
form also exists. All patients with DDS have point mutations in
the zinc finger domain encoded by exons 7 to 10 of theWT1gene
[19]. Most of them are missense and in exon 8 and 9 that encode
the second and third zinc fingers.
Moorthy et al. [20] proposed an allelic disorder known as Frasier
syndrome; characterised by a slowly progressing nephropathy,
male pseudohermaphroditism and no Wilms tumour [20]. Fo-
cal segmental glomerular sclerosis (FSGS) is often observed in
cases of Frasier syndrome meanwhile diffuse mesangial sclerosis
(DMS) is noted in Denys-Drash syndrome. Frasier syndrome
arises from heterozygous mutation at the intron 9 splicing donor
site of the WT1 gene [21,22].
The amount of the +KTS isoform is less as compared to −KTS
isoform owing to the intron 9 mutation in Frasier syndrome, in
whom masculinisation is impaired, suggestive of +KTS isoform
playing a role in masculinisation. The incidence of Wilms tu-
mour is considered to be markedly lower in patients with intron
9 mutations than in those with exonic mutations [23,24].
8. Postnatal
The genital malformations vary considerably, ranging from
penoscrotal hypospadias with bilateral cryptorchidism to an en-
larged clitoris with fused labia and a urogenital sinus, in patients
with a 46, XY karyotype. The internal genitalia may also be af-
fected; the abnormality varying from a small atrophic vagina and
uterus to the presence of streak ovaries or dysgenetic testes [25].
The nephropathy is characterized by onset of proteinuria be-
tween birth to two years of age [26]. With more than 50% of
children presenting with proteinuria before one year of age. Pro-
teinuria may evolve into nephrotic syndrome and to end stage
renal failure (ESRF) [27]. Varying degrees of focal and diffuse
mesangial sclerosis are the most consistent histopathological
findings in the kidneys. A 50% risk of developing Wilms’ tumor
has been reported in this syndrome [26].
3
Volume 1 Issue 1 -2018 Case Presentation
4. 9. Conclusion
Primary advantage of micro array is higher resolution which
yields more genetic information; array has been reported to iden-
tify additional clinical significant abnormality in approximately
6% of cases which might be missed on conventional karyotype.
Thus based on the results of NICHD multicentric trial 2012; pre-
natal chromosomal micro array analysis is most beneficial when
foetal structural abnormalities are detected on antenatal ultra-
sound [28].
In conclusion, there is a genotype phenotype concordance. Clini-
cal profile, progression of nephropathy, degree of genital abnor-
malities and incidence of Wilms tumours vary with the type of
underlying genetic mutation; i.e. exonic or intronic mutations.
Thus, detection of types of WT1 mutations is useful for prognos-
tic estimation of the clinical course in children with progressive
nephropathy.
It is important to consider the diagnosis of Denys-Drash syn-
drome in any patient with unexplained nephropathy, particularly
young girls and children with ambiguous genitalia or those pre-
senting with an early Wilms’ tumor.
References
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Hastie ND. Modulation of DNA binding specificity by alternative splic-
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VP, Rauscher FJ III. Repression of the insulin-like growth factor II gene
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degan M, Ross A, et al. Subnuclear localization of WT1 in splicing or
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14. Davies RC, Calvio C, Bratt E, Larsson SH, Lamond AI, Hastie ND.
WT1 interacts with the splicing factor U2AF65 in an isoform-depen-
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15. Jeanpierre C, Beroud C, Niaudet P, Junien C. Software and database
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17. Little M, Holmes G, Bickmore W, van Heyningen V, Hastie N,
Wainwright B. DNA binding capacity of the WT1 protein is abolished
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20. Moorthy AV, Chesney RW, Lubinsky M. Chronic renal failure and
XY gonadal dysgenesis:“Frasier”syndrome-acommentary on reported
cases. Am J Med Genet Suppl. 1987;3:297-302.
4
Volume 1 Issue 1 -2018 Case Presentation
5. 21. Kikuchi H, Takata A, Akasaka Y, Fukuzawa R, Yoneyama H, Kuro-
sawa Y, et al. Do intronic mutations aVecting splicing of WT1 exon 9
cause Frasier syndrome? J Med Genet. 1998;35:45-8.
22. Klamt B, Koziell A, Poulat F, Wieacker P, Scambler P, Berta P, et al.
Frasier syndrome is caused by defective alternative splicing of WT1
leading to an altered ratio of WT1 +/-KTS splice isoforms. Hum Mol
Genet. 1998;7:709-14.
23. König A, Jakubiczka S, Wieacker P, Schlosser HW, Gessler M. Fur-
ther evidence that imbalance of WT1 isoforms may be involved in De-
nys-Drash syndrome. Hum Mol Genet. 1993;2:1967-8.
24. Barbosa AS, Hadjiathanasiou CG, Theodoridis C, Papathanasiou A,
Tar A, Merksz M, et al. The same mutation aVecting the splicing of WT1
gene is present on Frasier syndrome patients with or without Wilms’
5
Volume 1 Issue 1 -2018 Case Presentation
tumor. Hum Mutat. 1999;13:146-53.
25. Coppes MJ, Campbell CR, Williams BRG. The role of WTI in
Wilms’ tumorigenesis. FASEB J. 1993;7: 886- 95.
26. Eddy AA, Mauer SM. Pseudoherma- phroditism, glomerulopathy
and Wilms’ tumor (Drash syndrome): fre- quency in end-stage renal
failure. J Pediatr. 1985;106:584-7.
27. Jadresic L, Leake J, Gordon I, Dillon MJ, Grant DB, Pritchard J, et
al. Clinicopathologic review of twelve children with%ephropathy,
Wilms’ tu- mor and genital abnormalities (Drash syndrome). J Pediatr.
1990;117:717725.
28. Wpner RJ, Martin CL, Levy B, Ballif BC, Eng Cm, Zachary Jm, et al.
Chromosomal microarray versus karyotyping for prenatal diagnosis. N
Engl J Med. 2012;367:2175-8.