scholarly journals PAX2 Mutation-Related Oligomeganephronia in a Young Adult Patient

2020 ◽  
Vol 10 (3) ◽  
pp. 163-173
Author(s):  
László Bitó ◽  
Tibor Kalmár ◽  
Zoltán Maróti ◽  
Sándor Turkevi-Nagy ◽  
Csaba Bereczki ◽  
...  
Keyword(s):  
English Language ◽  
De Novo ◽  
Enzyme Inhibitor ◽  
Genetic Diagnosis ◽  
Healthy Weight ◽  
Young Adult Patient ◽  
Normal Mean ◽  
History Of ◽  
Compensatory Enlargement ◽  
End Stage

Oligomeganephronic hypoplasia, commonly referred to as oligomeganephronia (OMN), is a rare pediatric disorder characterized by small kidneys. Histologically a paucity of nephrons is observed which show compensatory enlargement. Hyperfiltration injury leads to end-stage kidney disease. Here we report a 23-year-old Caucasian female patient who presented with a 7-year history of nonnephrotic proteinuria, slow worsening of renal function, normal-sized kidneys, normal blood pressure, healthy weight, and normoglycemia. Evaluation of a kidney biopsy specimen revealed sparsely distributed and markedly enlarged glomeruli (glomerular density 0.63/mm<sup>2</sup>, glomerular diameter 268 µm), focal segmental glomerulosclerosis (FSGS), and 70% effacement of the foot processes. The glomerular basement membrane was normal (mean thickness 285 nm). The genetic analysis of 19 genes known to cause FSGS identified a heterozygous de novo nonsense mutation of <i>PAX2</i> in exon 4 (NM_003990.3:c.430C&#x3e;T and NP_003981.2:p.Gln144Ter). Clinical investigations ruled out optic nerve coloboma, hearing loss, and vesicoureteral reflux. Magnetic resonance imaging of the urogenital tract found the uterus to be bicornuate. Based on these data, OMN in nonhypoplastic kidneys and adaptive FSGS related to <i>PAX2</i> mutation was diagnosed. Her kidney function worsened during the 30-month follow-up (last visit: eGFR-EPI 32 mL/min/1.73 m<sup>2</sup>) despite angiotensin-converting enzyme inhibitor treatment. To our best knowledge, our patient is the seventh in the English-language literature with a biopsy diagnosis of OMN in an adult, the first observed with normal-sized kidneys, and the first in whom a specific etiologic genetic diagnosis was established. Nonsense <i>PAX2</i> mutations between the paired domain and the octapeptide domain appear to manifest in renal-limited phenotype.

scholarly journals Severe Generalized Epidermolysis Bullosa Simplex in Two Hong Kong Children due to De Novo Variants in KRT14 and KRT5

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Shuk Ching Chong ◽  
Kam Lun Hon ◽  
Fernando Scaglia ◽  
Chung Mo Chow ◽  
Yu Ming Fu ◽  
...  
Keyword(s):  
Hong Kong ◽  
Epidermolysis Bullosa ◽  
De Novo ◽  
Genetic Diagnosis ◽  
Recurrence Risk ◽  
Severe Form ◽  
Epidermolysis Bullosa Simplex ◽  
First Case ◽  
Heterozygous Variant ◽  
History Of

We report two Hong Kong children with severe generalized epidermolysis bullosa simplex (EBS), the most severe form of EBS, without a family history of EBS. EBS is a rare genodermatosis usually inherited in an autosomal dominant fashion although rare autosomal recessive cases have been reported. Genetic studies in these patients showed that the first case was due to a novel de novo heterozygous variant, c.377T>G (NM_000526.5 (c.377T>G, p.Leu126Arg)) in the KRT14 gene and the second case was due to a rare de novo heterozygous variant c.527A>G (NM_000424.4, c.527A>G, p.Asn176Ser) in the KRT5 gene. To our knowledge, the c.377T>G variant in the KRT14 gene has not been previously reported, and the c.527A>G variant in the KRT5 gene is a rare cause of severe generalized EBS. In severe generalized EBS, infants exhibit severe symptoms at the onset; however, they tend to improve with time. A precise genetic diagnosis in these two cases aided in counseling the families concerning the prognosis in their affected children and the recurrence risk for future pregnancies.

scholarly journals Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations

2010 ◽  
Vol 162 (5) ◽  
pp. 987-992 ◽  
Author(s):  
S E Flanagan ◽  
R R Kapoor ◽  
G Mali ◽  
D Cody ◽  
N Murphy ◽  
...  
Keyword(s):  
Family History ◽  
De Novo ◽  
Clinical Phenotype ◽  
Mutation Screening ◽  
Genetic Diagnosis ◽  
Gene Mutations ◽  
Hyperinsulinemic Hypoglycemia ◽  
Neonatal Hypoglycemia ◽  
Family History Of Diabetes ◽  
History Of

ObjectiveThe phenotype associated with heterozygous HNF4A gene mutations has recently been extended to include diazoxide responsive neonatal hypoglycemia in addition to maturity-onset diabetes of the young (MODY). To date, mutation screening has been limited to patients with a family history consistent with MODY. In this study, we investigated the prevalence of HNF4A mutations in a large cohort of patients with diazoxide responsive hyperinsulinemic hypoglycemia (HH).Subjects and methodsWe sequenced the ABCC8, KCNJ11, GCK, GLUD1, and/or HNF4A genes in 220 patients with HH responsive to diazoxide. The order of genetic testing was dependent upon the clinical phenotype.ResultsA genetic diagnosis was possible for 59/220 (27%) patients. KATP channel mutations were most common (15%) followed by GLUD1 mutations causing hyperinsulinism with hyperammonemia (5.9%), and HNF4A mutations (5%). Seven of the 11 probands with a heterozygous HNF4A mutation did not have a parent affected with diabetes, and four de novo mutations were confirmed. These patients were diagnosed with HI within the first week of life (median age 1 day), and they had increased birth weight (median +2.4 SDS). The duration of diazoxide treatment ranged from 3 months to ongoing at 8 years.ConclusionsIn this large series, HNF4A mutations are the third most common cause of diazoxide responsive HH. We recommend that HNF4A sequencing is considered in all patients with diazoxide responsive HH diagnosed in the first week of life irrespective of a family history of diabetes, once KATP channel mutations have been excluded.

The Nonviolent Struggle for Indian Freedom, 1905-19

2018 ◽  
Author(s):  
David Hardiman
Keyword(s):  
English Language ◽  
Second World War ◽  
World War ◽  
Passive Resistance ◽  
Civil Resistance ◽  
Political Concept ◽  
History Of ◽  
Second World ◽  
Moral Stance

Much of the recent surge in writing about the practice of nonviolent forms of resistance has focused on movements that occurred after the end of the Second World War, many of which have been extremely successful. Although the fact that such a method of civil resistance was developed in its modern form by Indians is acknowledged in this writing, there has not until now been an authoritative history of the role of Indians in the evolution of the phenomenon.The book argues that while nonviolence is associated above all with the towering figure of Mahatma Gandhi, 'passive resistance' was already being practiced as a form of civil protest by nationalists in British-ruled India, though there was no principled commitment to nonviolence as such. The emphasis was on efficacy, rather than the ethics of such protest. It was Gandhi, first in South Africa and then in India, who evolved a technique that he called 'satyagraha'. He envisaged this as primarily a moral stance, though it had a highly practical impact. From 1915 onwards, he sought to root his practice in terms of the concept of ahimsa, a Sanskrit term that he translated as ‘nonviolence’. His endeavors saw 'nonviolence' forged as both a new word in the English language, and as a new political concept. This book conveys in vivid detail exactly what such nonviolence entailed, and the formidable difficulties that the pioneers of such resistance encountered in the years 1905-19.

Repainting the Little Red Schoolhouse

2002 ◽  
Author(s):  
John G. Rodden
Keyword(s):  
Educational Reform ◽  
English Language ◽  
Nation Building ◽  
German Education ◽  
Language Study ◽  
History Of

This is the first English-language study of GDR education and the first book, in any language, to trace the history of Eastern German education from 1945 through the 1990s. Rodden fully relates the GDR's attempt to create a new Marxist nation by means of educational reform, and looks not only at the changing institution of education but at something the Germans call Bildung--the formation of character and the cultivation of body and spirit. The sociology of nation-building is also addressed.

Canada

2018 ◽  
Author(s):  
George L. Parker
Keyword(s):  
New York ◽  
English Language ◽  
Book Market ◽  
Canadian Literature ◽  
History Of ◽  
Queen's University ◽  
American Authors

This chapter discusses the history of fiction publishing in Canada since 1950. It begins with the arrival of New York publisher Alfred Knopf in Canada in August 1955, a month after the Canadian Writers' Conference was held at Queen's University in Kingston, Ontario. During the conference, the sorry plight of the English-language book scene was tackled: bookstores, for example, were dominated by British and American authors, and Canadian literature was practically ignored in schools and universities. The chapter examines how many of these complaints were resolved by the 2000s. It considers changes in Canadian fiction from traditional realism towards modernism and postmodernism, and the importance of the New Canadian Library quality paperback series (1958). It also describes other significant developments that reshaped the Canadian book market, including the emergence of independent small presses, Harlequin Enterprises, the proliferation of international conglomerates, the marketing of e-books, and the rise of Amazon.

The Oxford History of the Novel in English

2018 ◽  
Keyword(s):  
World War Ii ◽  
English Language ◽  
Book History ◽  
World Order ◽  
The United States ◽  
The Novel ◽  
History Of The Novel ◽  
Post Colonial ◽  
The World ◽  
History Of

Volume Nine of this series traces the development of the ‘world novel’, that is, English-language novels written throughout the world, beyond Britain, Ireland, and the United States. Focusing on the period up to 1950, the volume contains survey chapters and chapters on major writers, as well as chapters on book history, publishing, and the critical contexts of the work discussed. The text covers periods from renaissance literary imaginings of exotic parts of the world like Oceania, through fiction embodying the ideology and conventions of empire, to the emergence of settler nationalist and Indigenous movements and, finally, the assimilations of modernism at the beginnings of the post-imperial world order. The book, then, contains chapters on the development of the non-metropolitan novel throughout the British world from the eighteenth to the mid twentieth centuries. This is the period of empire and resistance to empire, of settler confidence giving way to doubt, and of the rise of indigenous and post-colonial nationalisms that would shape the world after World War II.

scholarly journals R1352Q CACNA1A Variant in a Patient with Sporadic Hemiplegic Migraine, Ataxia, Seizures and Cerebral Oedema: A Case Report

2021 ◽  
pp. 123-130
Author(s):  
Anker Stubberud ◽  
Emer O’Connor ◽  
Erling Tronvik ◽  
Henry Houlden ◽  
Manjit Matharu
Keyword(s):  
Mental Retardation ◽  
Case Report ◽  
Genetic Testing ◽  
Head Trauma ◽  
Cerebral Oedema ◽  
De Novo ◽  
Minor Head Trauma ◽  
Hemiplegic Migraine ◽  
Wide Range ◽  
History Of

Mutations in the <i>CACNA1A</i> gene show a wide range of neurological phenotypes including hemiplegic migraine, ataxia, mental retardation and epilepsy. In some cases, hemiplegic migraine attacks can be triggered by minor head trauma and culminate in encephalopathy and cerebral oedema. A 37-year-old male without a family history of complex migraine experienced hemiplegic migraine attacks from childhood. The attacks were usually triggered by minor head trauma, and on several occasions complicated with encephalopathy and cerebral oedema. Genetic testing of the proband and unaffected parents revealed a de novo heterozygous nucleotide missense mutation in exon 25 of the <i>CACNA1A</i> gene (c.4055G&#x3e;A, p.R1352Q). The R1352Q <i>CACNA1A</i> variant shares the phenotype with other described <i>CACNA1A</i> mutations and highlights the interesting association of trauma as a precipitant for hemiplegic migraine. Subjects with early-onset sporadic hemiplegic migraine triggered by minor head injury or associated with seizures, ataxia or episodes of encephalopathy should be screened for mutations. These patients should also be advised to avoid activities that may result in head trauma, and anticonvulsants should be considered as prophylactic migraine therapy.

scholarly journals Sequential fate-switches in stem-like cells drive the tumorigenic trajectory from human neural stem cells to malignant glioma

Cell Research ◽  
2021 ◽  
Author(s):  
Xiaofei Wang ◽  
Ran Zhou ◽  
Yanzhen Xiong ◽  
Lingling Zhou ◽  
Xiang Yan ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Single Cell ◽  
De Novo ◽  
Early Stage ◽  
Lineage Tracing ◽  
Human Neural Stem Cells ◽  
Transcriptional Reprogramming ◽  
Neural Stem Progenitor Cells ◽  
Human Gbm ◽  
End Stage

AbstractGlioblastoma (GBM) is an incurable and highly heterogeneous brain tumor, originating from human neural stem/progenitor cells (hNSCs/hNPCs) years ahead of diagnosis. Despite extensive efforts to characterize hNSCs and end-stage GBM at bulk and single-cell levels, the de novo gliomagenic path from hNSCs is largely unknown due to technical difficulties in early-stage sampling and preclinical modeling. Here, we established two highly penetrant hNSC-derived malignant glioma models, which resemble the histopathology and transcriptional heterogeneity of human GBM. Integrating time-series analyses of whole-exome sequencing, bulk and single-cell RNA-seq, we reconstructed gliomagenic trajectories, and identified a persistent NSC-like population at all stages of tumorigenesis. Through trajectory analyses and lineage tracing, we showed that tumor progression is primarily driven by multi-step transcriptional reprogramming and fate-switches in the NSC-like cells, which sequentially generate malignant heterogeneity and induce tumor phenotype transitions. We further uncovered stage-specific oncogenic cascades, and among the candidate genes we functionally validated C1QL1 as a new glioma-promoting factor. Importantly, the neurogenic-to-gliogenic switch in NSC-like cells marks an early stage characterized by a burst of oncogenic alterations, during which transient AP-1 inhibition is sufficient to inhibit gliomagenesis. Together, our results reveal previously undercharacterized molecular dynamics and fate choices driving de novo gliomagenesis from hNSCs, and provide a blueprint for potential early-stage treatment/diagnosis for GBM.

Sign in / Sign up

Export Citation Format

Share Document