Vulnerability to Meningococcal Disease in Immunodeficiency Due to a Novel Pathogenic Missense Variant in NFKB1

NF-κB1 deficiency is suggested to be the most common cause of common variable immunodeficiency (CVID). NFKB1 encodes for the p105 precursor protein of NF-κB1, which is converted into the active transcriptional subunit p50 through proteasomal processing of its C-terminal half upon stimulation and is implicated in the canonical NF-kB pathway. Rare monoallelic NFKB1 variants have been shown to cause (haplo) insufficiency. Our report describes a novel NFKB1 missense variant (c.691C>T, p.R230C; allele frequency 0.00004953) in a family vulnerable to meningitis, sepsis, and late-onset hypogammaglobulinemia. We investigated the pathogenic relevance of this variant by lymphocyte stimulation, immunophenotyping, overexpression study and immunoblotting. The ectopic expression of p50 for c.691 C>T restricted transcriptionally active p50 in the cytoplasm, and immunoblotting revealed reduced p105/50 expression. This study shows that the deleterious missense variant in NFKB1 adversely affects the transcriptional and translational activity of NFκB1, impairing its function. Patients immunological parameters show a progressive course of hypogammaglobulinemia, which may partially account for the incomplete disease penetrance and suggest the need for closer immunological monitoring of those mutation carriers.

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A Cross-Sectional Observational Study on Neonatal Thrombocytopenia in a Teaching Hospital in Telangana

Journal of Evidence Based Medicine and Healthcare ◽

10.18410/jebmh/2021/65 ◽

2021 ◽

Vol 8 (06) ◽

pp. 337-341

Author(s):

Rajesh Khanna Pulmamidi ◽

Ramya Madhuri Yendamuri

Keyword(s):

Observational Study ◽

Teaching Hospital ◽

Neonatal Sepsis ◽

Late Onset ◽

Birth Asphyxia ◽

Predisposing Factors ◽

Maternal Factors ◽

Cross Sectional ◽

Common Cause ◽

Neonatal Thrombocytopenia

BACKGROUND Neonatal thrombocytopenia is one of the most common haematological abnormalities in neonates occurring in 1 to 2 % of healthy term neonates. Various risk factors like sepsis, prematurity, and birth asphyxia are known to be associated with this condition. Maternal factors also predispose to this condition. Early detection and appropriate management is of utmost importance to prevent complications. The aim of the study is to evaluate the predisposing factors for neonatal thrombocytopenia in a teaching hospital. METHODS This was a cross sectional observational study done in the Department of Peadiatrics, MediCiti Institute of Medical Sciences, Medchal, Telangana, for a duration of one year i.e., from January 2019 to December 2019. A total of 60 neonates with thrombocytopenia were studied for onset of thrombocytopenia, severity based on platelet counts, aetiology and for contributing maternal factors. RESULTS Early onset thrombocytopenia (< 3 days of age) was seen in 46.6 % (28 / 60) and late onset thrombocytopenia (3 - 28 days) in 53.3 % (32 / 60). The most common cause for neonatal thrombocytopenia was neonatal sepsis 30 % (10 / 60), followed by birth asphyxia. Common maternal predisposing factors were pregnancyinduced hypertension and pregnancy-induced diabetes mellitus. CONCLUSIONS Neonatal thrombocytopenia is one of the most common clinical problems in neonates. It can be of early or late onset type and has fetal and maternal predisposing factors. Neonatal sepsis is one of the most common cause for neonatal thrombocytopenia followed by birth asphyxia which is a preventable cause. Early diagnosis and thorough evaluation are needed to prevent complications. KEYWORDS Neonatal Thrombocytopenia, Neonatal Sepsis

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Antenatally Diagnosed Posterior Urethral Valve: A Case Report

Community Based Medical Journal ◽

10.3329/cbmj.v5i1.53920 ◽

2016 ◽

Vol 5 (1) ◽

pp. 42-45

Author(s):

Mahzabeen Islam ◽

Masudur Rahman ◽

Sankar Narayan Dey ◽

Netay Kumer Sharma ◽

Mir Naz Farzana

Keyword(s):

Clinical Presentation ◽

Antenatal Diagnosis ◽

Late Onset ◽

Obstructive Uropathy ◽

Lower Abdominal Pain ◽

Posterior Urethral Valve ◽

Caesarian Section ◽

Common Cause ◽

Obstructive Lesion ◽

Urethral Valve

Posterior urethral valve (PUV) are the most common congenital obstructive lesion of the urethra and a common cause of obstructive uropathy in infancy. Clinical presentation depends on the severity of the obstruction. In case of severe obstruction, the diagnosis is usually made antenatally. Here, we present a case of antenatally diagnosed PUV of a fetus of a lady in her 9th month of pregnancy with mild lower abdominal pain for several hours. On ultrasound (US) examination, we found 36.5±2 weeks of pregnancy with mild to moderate oligohydramnios. Fetal urinary bladder was over distended; both the kidneys were grossly hydronephrotic and PUV like echo lucent area was seen at the prostatic region (Key hole sign). Emergency caesarian section (CS) was done and US of the baby showed typical US finding of PUV. The prognosis of antenatal diagnosis of PUV in early pregnancy is poor. But in this case due to the late onset of symptoms and as immediate necessary steps were taken, the baby was totally cured. This case was reported to aware about importance of antenatal anomaly scan and to share our experience. CBMJ 2016 January: Vol. 05 No. 01 P: 42-45

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Upper GI Bleed, Etiology, Role of Endoscopy in Rural Population of Punjab

International Journal of Computational Models and Algorithms in Medicine ◽

10.4018/jcmam.2010070103 ◽

2010 ◽

Vol 1 (3) ◽

pp. 55-68 ◽

Cited By ~ 1

Author(s):

Ravinder Singh Malhotra ◽

K. S. Ded ◽

Arun Gupta ◽

Darpan Bansal ◽

Harneet Singh

Keyword(s):

Peptic Ulcer ◽

Gastrointestinal Bleeding ◽

Upper Gastrointestinal Bleeding ◽

Common Cause ◽

Endoscopic Techniques ◽

Gi Bleed ◽

Upper Gastrointestinal ◽

Common Variable ◽

Important Progress

Haematemesis and malena are the two most important symptoms of upper gastrointestinal bleeding . The most common cause of upper gastrointestinal bleeding is due to a peptic ulcer. In this paper, the authors research the cause of bleeding. Contrary to previous studies, results favor esophageal varices, e.g., alcoholism or cirrhosis liver post necrotic, as the most common cause of bleeding rather than a peptic ulcer. The authors’ study is based on an observational retrospective protocol with records of 50 consecutive patients with GI bleeding, attending the emergency room from February 2007 until September 2009. Results show that the treatment of UGI bleeding has made important progress since the introduction of emergency endoscopy and endoscopic techniques for haemostasis. The application of specific protocols significantly decreases rebleeding and the need for surgery, whereas mortality is still high. The data highlight the decreasing trend of peptic ulcer as the sole cause of bleeding, as shown in previous literature, ascertaining that varices are now the most common variable.

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Analysis of the LRRK2 p.G2019S mutation in Colombian Parkinson’s Disease Patients

Colombia Medica ◽

10.25100/cm.v46i3.1553 ◽

2015 ◽

pp. 117-121 ◽

Cited By ~ 6

Author(s):

Andres Felipe Duque ◽

Juan Carlos Lopez ◽

Helena Hernandez ◽

Bruno Benitez ◽

Juan Jose Yunis ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson Disease ◽

Latin American ◽

Autosomal Dominant ◽

Late Onset ◽

Causal Factor ◽

Leucine Rich Repeat ◽

Common Cause ◽

Asymptomatic Control ◽

Normal Controls

Introduction: Mutations in the leucine-rich repeat kinase 2 gene (LRRK2 or Dardarin) are considered to be a common cause of autosomal dominant and sporadic Parkinson´s disease, but the prevalence of these mutations varies among populations. Objective: to analysed the frequency of the LRRK2 p.G2019S mutation (c.6055G>A transition) in a sample of Colombian patients. Materials and Methods: In the present study we have analysed the frequency of the LRRK2 p.G2019S mutation in 154 patients with familial or sporadic Parkinson Disease, including early and late onset patients, and 162 normal controls. Results: Our results show occurrence of this mutation in two cases (2/154, 1.3%) with classical Parkinson´s signs, and one completely asymptomatic control (1/162, 0.6%). Conclusion: The p.G2019S mutation is not an important causal factor of Parkinson Disease in Colombia having similar frequencies to those reported in other Latin American populations.

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CANVAS: a late onset ataxia due to biallelic intronic AAGGG expansions

Journal of Neurology ◽

10.1007/s00415-020-10183-0 ◽

2020 ◽

Author(s):

Natalia Dominik ◽

Valentina Galassi Deforie ◽

Andrea Cortese ◽

Henry Houlden

Keyword(s):

Late Onset ◽

Replication Factor C ◽

Common Cause ◽

Progressive Ataxia ◽

The World ◽

Recent Developments ◽

C Subunit ◽

Repeat Expansions ◽

Visual Problems ◽

Factor C

Abstract The ataxias are a group of disorders that manifest with balance, movement, speech and visual problems. They can arise due to dysfunction of the cerebellum, the vestibular system and/or the sensory neurons. Genetic defects are a common cause of chronic ataxia, particularly common are repeat expansions in this group of conditions. Co-occurrence of cerebellar ataxia with neuropathy and vestibular areflexia syndrome has been termed CANVAS. Although CANVAS is a rare syndrome, on discovery of biallelic expansions in the second intron of replication factor C subunit 1 (RFC1) gene, we and others have found the phenotype is broad and RFC1 expansions are a common cause of late-onset progressive ataxia. We aim to provide a review and update on recent developments in CANVAS and populations, where the disorder has been reported. We have also optimised a protocol for RFC1 expansion screening which is described herein and expanded phenotype after analysing late-onset ataxia patients from around the world.

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Selective Disruption of “Late Onset” Sagittal Banding Patterns by Ectopic Expression of Engrailed-2 in Cerebellar Purkinje Cells

Journal of Neuroscience ◽

10.1523/jneurosci.19-13-05370.1999 ◽

1999 ◽

Vol 19 (13) ◽

pp. 5370-5379 ◽

Cited By ~ 52

Author(s):

Stephan L. Baader ◽

Michael W. Vogel ◽

Salih Sanlioglu ◽

Xulun Zhang ◽

John Oberdick

Keyword(s):

Purkinje Cells ◽

Late Onset ◽

Ectopic Expression ◽

Banding Patterns ◽

Cerebellar Purkinje Cells

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A rare missense variant of CASP7 is associated with familial late-onset Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2018.10.005 ◽

2018 ◽

Vol 15 (3) ◽

pp. 441-452 ◽

Cited By ~ 10

Author(s):

Xiaoling Zhang ◽

Congcong Zhu ◽

Gary Beecham ◽

Badri N. Vardarajan ◽

Yiyi Ma ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Late Onset ◽

Missense Variant

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Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia

Nature Genetics ◽

10.1038/s41588-019-0372-4 ◽

2019 ◽

Vol 51 (4) ◽

pp. 649-658 ◽

Cited By ~ 81

Author(s):

Andrea Cortese ◽

Roberto Simone ◽

Roisin Sullivan ◽

Jana Vandrovcova ◽

Huma Tariq ◽

...

Keyword(s):

Late Onset ◽

Common Cause

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Rapidly progressive course of very late onset multiple sclerosis presenting with Parkinsonism: case report

Multiple Sclerosis Journal ◽

10.1177/1352458510384306 ◽

2010 ◽

Vol 17 (2) ◽

pp. 245-249 ◽

Cited By ~ 9

Author(s):

T Schultheiss ◽

H Reichmann ◽

T Ziemssen

Keyword(s):

Multiple Sclerosis ◽

Potential Benefit ◽

Late Onset ◽

Age Groups ◽

Treatment Strategies ◽

Disease Course ◽

Spastic Paraplegia ◽

Diagnostic Challenge ◽

Progressive Course ◽

Neuroprotective Therapies

Multiple sclerosis mainly affects young adolescents, making late-onset multiple sclerosis a rarity and diagnostic challenge, particularly for cases after age 80 years. We present an 82-year-old patient with multiple sclerosis with very late onset. As well as spastic paraplegia, additional Parkinsonism secondary to demyelination in the basal ganglia was observed in this case. In most publications, spinal cord lesions were more common in late-onset multiple sclerosis which, in contrast, could not be found in our case. Despite different treatment strategies, rapid clinical deterioration and death after about 2 years of disease course occurred. Further discrimination in late-onset multiple sclerosis (50–70 years) and multiple sclerosis with very late onset (above 70 years) might be considered. Future trials to elucidate potential benefit of immunosuppressive (and neuroprotective) therapies in these age groups are mandatory.

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