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Cerebrovascular Diseases (Basel,... 2022Moyamoya disease is characterized by progressive stenotic changes in the terminal segment of the internal carotid artery and the development of abnormal vascular...
INTRODUCTION
Moyamoya disease is characterized by progressive stenotic changes in the terminal segment of the internal carotid artery and the development of abnormal vascular networks called moyamoya vessels. The objective of this review was to provide a holistic view of the epidemiology, etiology, clinical findings, treatment, and pathogenesis of moyamoya disease. A literature search was performed in PubMed using the term "moyamoya disease," for articles published until 2021.
RESULTS
Artificial intelligence (AI) clustering was used to classify the articles into 5 clusters: (1) pathophysiology (23.5%); (2) clinical background (37.3%); (3) imaging (13.2%); (4) treatment (17.3%); and (5) genetics (8.7%). Many articles in the "clinical background" cluster were published from the 1970s. However, in the "treatment" and "genetics" clusters, the articles were published from the 2010s through 2021. In 2011, it was confirmed that a gene called Ringin protein 213 (RNF213) is a susceptibility gene for moyamoya disease. Since then, tremendous progress in genomic, transcriptomic, and epigenetic profiling (e.g., methylation profiling) has resulted in new concepts for classifying moyamoya disease. Our literature survey revealed that the pathogenesis involves aberrations of multiple signaling pathways through genetic mutations and altered gene expression.
CONCLUSION
We analyzed the content vectors in abstracts using AI, and reviewed the pathophysiology, clinical background, radiological features, treatments, and genetic peculiarity of moyamoya disease.
Topics: Adenosine Triphosphatases; Artificial Intelligence; Genetic Predisposition to Disease; Humans; Moyamoya Disease; Ubiquitin-Protein Ligases
PubMed: 35104814
DOI: 10.1159/000520099 -
Frontiers in Oncology 2022Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal bone-marrow diseases with ineffective hematopoiesis resulting in cytopenias and morphologic dysplasia...
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal bone-marrow diseases with ineffective hematopoiesis resulting in cytopenias and morphologic dysplasia of hematopoietic cells. MDS carry a wide spectrum of genetic abnormalities, ranging from chromosomal abnormalities such as deletions/additions, to recurrent mutations affecting the spliceosome, epigenetic modifiers, or transcription factors. As opposed to AML, research in MDS has been hindered by the lack of preclinical models that faithfully replicate the complexity of the disease and capture the heterogeneity. The complex molecular landscape of the disease poses a unique challenge when creating transgenic mouse-models. In addition, primary MDS cells are difficult to manipulate limiting studies and resulting in a paucity of cell lines and patient derived xenograft models. In recent years, progress has been made in the development of both transgenic and xenograft murine models advancing our understanding of individual contributors to MDS pathology as well as the complex primary interplay of genetic and microenvironment aberrations. We here present a comprehensive review of these transgenic and xenograft models for MDS and future directions.
PubMed: 35372085
DOI: 10.3389/fonc.2022.815037 -
Neuromuscular Disorders : NMD Dec 2017Infantile or early onset is estimated to occur in around 10% of all facioscapulohumeral dystrophy (FSHD) patients. Although small series of early onset FSHD patients... (Review)
Review
Infantile or early onset is estimated to occur in around 10% of all facioscapulohumeral dystrophy (FSHD) patients. Although small series of early onset FSHD patients have been reported, comprehensive data on the clinical phenotype is missing. We performed a systematic literature search on the clinical features of early onset FSHD comprising a total of 43 articles with individual data on 227 patients. Additional data from four cohorts was provided by the authors. Mean age at reporting was 18.8 years, and 40% of patients were wheelchair-dependent at that age. Half of the patients had systemic features, including hearing loss (40%), retinal abnormalities (37%) and developmental delay (8%). We found an inverse correlation between repeat size and disease severity, similar to adult-onset FSHD. De novo FSHD1 mutations were more prevalent than in adult-onset FSHD. Compared to adult FSHD, our findings indicate that early onset FSHD is overall characterized by a more severe muscle phenotype and a higher prevalence of systemic features. However, similar as in adults, a significant clinical heterogeneity was observed. Based on this, we consider early onset FSHD to be on the severe end of the FSHD disease spectrum. We found natural history studies and treatment studies to be very scarce in early onset FSHD, therefore longitudinal studies are needed to improve prognostication, clinical management and trial-readiness.
Topics: Adult; Age of Onset; Child; Humans; Infant; Muscular Dystrophy, Facioscapulohumeral
PubMed: 29102079
DOI: 10.1016/j.nmd.2017.09.007 -
British Journal of Cancer Feb 2005We performed a systematic review of studies that investigated the effect of abnormalities of the tumour suppressor gene p53 upon prognosis in patients with colorectal... (Review)
Review
We performed a systematic review of studies that investigated the effect of abnormalities of the tumour suppressor gene p53 upon prognosis in patients with colorectal cancer. The methods used to assess p53 status were immunohistochemistry (IHC), indicating abnormal accumulation of p53, and sequence analysis, indicating presence of p53 mutations (mut). We identified 168 reports, with 241 comparisons of relevant end points and survival data on 18 766 patients. We found evidence of both publication bias and heterogeneity of results. Our analysis was hampered by variability in both the assessment of p53 status and the reporting of results. We used a trim and fill method to correct for publication bias and minimised heterogeneity by using well-defined clinical subgroups for the assessment of outcomes. Overall, patients with abnormal p53 were at increased risk of death: relative risk (RR) with IHC 1.32 (95% confidence interval (c.i.) 1.23-1.42) and with mutation analysis 1.31 (95% c.i. 1.19-1.45). The adverse impact of abnormal p53 was greater in patients with lower baseline risk of dying: good prognosis RR (mut) 1.63 (95% c.i. 1.40-1.90) and poor prognosis RR (mut) 1.04 (95% c.i. 0.91-1.19). We found no effect of abnormal p53 on outcome in patients treated with chemotherapy. Abnormal p53 was associated with failure of response to radiotherapy in patients with rectal cancer: RR (mut) 1.49 (95% c.i. 1.25-1.77).
Topics: Bias; Colorectal Neoplasms; Genes, p53; Humans; Immunohistochemistry; Mutation; Prognosis; Rectal Neoplasms; Regression Analysis; Survival Analysis; Tumor Suppressor Protein p53
PubMed: 15668707
DOI: 10.1038/sj.bjc.6602358 -
The Cochrane Database of Systematic... Aug 2019Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains...
BACKGROUND
Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains cause haemolytic anaemia by causing membrane damage and cell death within organ systems and destruction of erythroid precursors in the bone marrow. The life-long management of the general health effects of thalassaemia in affected individuals is a highly challenging issue in and of itself; and failure to deal with dental and orthodontic complications in people with thalassaemia exacerbates the public health, financial and personal burden posed by the condition. There exists a lack of evidence-based guidelines for care-seekers and providers to best deal with such dental and orthodontic complications in thalassaemia, which this review seeks to address.
OBJECTIVES
The main objective of this review was to assess different methods to treat dental and orthodontic complications in people with thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We searched the reference lists of relevant articles and reviews.Date of last search: 01 August 2019.We also searched nine online databases (PubMed, Google Scholar, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Literature in the Health Sciences in Latin America and the Caribbean database, African Index Medicus, Index Medicus for South East Asia Region, Index Medicus for the Eastern Mediterranean Region, Indexing of Indian Medical Journals). We searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organizations, pharmaceutical companies and researchers working in this field.Date of last search: 22 July 2019.
SELECTION CRITERIA
We searched for published or unpublished randomised controlled trials for treatment of dental and orthodontic complications in individuals diagnosed with thalassaemia, irrespective of phenotype, severity, age, gender and ethnic origin.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened 35,202 titles from search results. We identified four unique randomised controlled trials, of which one seemed potentially relevant. Based on closer inspection, the trial was found not to be eligible for inclusion.
MAIN RESULTS
We did not find any relevant trials for inclusion in the review.
AUTHORS' CONCLUSIONS
We were unable to draw any conclusions due to the lack of available data and trials. This review highlights the need for conducting and appropriate reporting, of high-quality randomised controlled trials investigating the effectiveness of various treatment modalities for dental and orthodontic complications in people with thalassaemia.
Topics: Humans; Malocclusion; Randomized Controlled Trials as Topic; Thalassemia; Tooth Diseases
PubMed: 31425614
DOI: 10.1002/14651858.CD012969.pub2 -
The Libyan Journal of Medicine Jun 2013Wolcott-Rallison syndrome (WRS) is caused by recessive EIF2AK3 gene mutations and characterized by permanent neonatal diabetes (PNDM), skeletal dysplasia, and recurrent... (Review)
Review
BACKGROUND
Wolcott-Rallison syndrome (WRS) is caused by recessive EIF2AK3 gene mutations and characterized by permanent neonatal diabetes (PNDM), skeletal dysplasia, and recurrent hepatitis. The frequency of this rare syndrome is largely unknown.
OBJECTIVES
To define the frequency and spectrum of WRS in the Kingdom of Saudi Arabia (KSA) based on published data.
METHODS
The Medline database was searched for published articles on WRS. The number of reported cases from KSA was compared to the total number of WRS cases reported worldwide. The genotype and phenotype of WRS patients from KSA were reviewed.
RESULTS
Ten articles describing 23 WRS patients from 12 Saudi families from 1995 to 2012 were identified. This figure accounts for 27.7% (23/83) of the patients and 22.2% (12/54) of the families with WRS reported worldwide until January 2013. All Saudi patients with WRS presented with PNDM, and they represent 59% of all PNDM cases from WRS. At reporting, 73% of patients experienced recurrent hepatitis, 56.5% had skeletal abnormalities, and 39.1% of them were dead. There was a variation in the phenotype even between affected siblings. Genetic diagnosis was confirmed in all 12 families with no correlation between the genotype and phenotype. Eight of the nine EIF2AK3 mutations were only reported in these families, and one was shared with a patient from Qatar, a neighboring Arab state.
CONCLUSIONS
No study on the frequency of WRS has been published. However, the available data indicate that KSA has the largest collection of patients with WRS worldwide, and nine of the identifiable EIF2AK3 mutations appear to be confined to Arabs. Establishing a national or international registry for WRS would provide more reliable data on this rare condition.
Topics: Age of Onset; Child; Child, Preschool; Diabetes Mellitus, Type 1; Epiphyses; Female; Genotype; Humans; Infant; Infant, Newborn; Male; Mutation; Osteochondrodysplasias; Phenotype; Prognosis; Saudi Arabia; eIF-2 Kinase
PubMed: 23759358
DOI: 10.3402/ljm.v8i0.21137 -
Seizure Jul 2022IRF2BPL is an intronless gene that was mapped to 14q24.3 chromosome in 2000 and codes for the interferon regulatory factor 2 binding like protein. (Review)
Review
BACKGROUND
IRF2BPL is an intronless gene that was mapped to 14q24.3 chromosome in 2000 and codes for the interferon regulatory factor 2 binding like protein.
OBJECTIVE
To analyses the clinical characteristics of the patients reported in the literature and of an additional patient we observed in order to better delineate the phenomenological spectrum of the disease and provide indications to improve clinical recognition and facilitate diagnosis.
METHODS
We reported on 28 patients carrying the IRF2BPL mutation who were identified in 10 papers (n.27), using PUBMED as the search engine, and in our hospital (n. 1).
RESULTS
All patients shared developmental delay/regression. Additional neurological symptoms were present in a large proportion of patients and reflected the involvement of five main neurological domains, i.e. epilepsy, dystonia, ataxia, spasticity, and ocular disturbances. Correlation analysis suggested a significant positive correlation between the number of affected neurological domains and the presence of MRI abnormalities (rho = 0.45, p = 0.02), while no significant correlation emerged between the number of affected clinical domains and age at disease onset (rho = 0.18, p = 0.35) or variant type (rho = 0.30, p = 0.12).
CONCLUSIONS
Our analysis highlights that the IRF2BPL mutation syndrome is highly specific to the central nervous system. Diagnostic work-up should consider the clinical picture of the IRF2BPL mutation syndrome herein delineated and the existence of conditions that share developmental delay/regression and result from acquired/genetic or unidentifiable underlying etiology.
Topics: Carrier Proteins; Dystonic Disorders; Epilepsy; Humans; Mutation; Nuclear Proteins; Syndrome
PubMed: 35525099
DOI: 10.1016/j.seizure.2022.04.010 -
Seminars in Perinatology Mar 2019Genetic abnormalities, whether occurring in the conceptus or the parents, can predispose to sporadic or recurrent pregnancy loss (RPL). Abnormalities in the conceptus...
Genetic abnormalities, whether occurring in the conceptus or the parents, can predispose to sporadic or recurrent pregnancy loss (RPL). Abnormalities in the conceptus include aneuploidy, copy number changes, skewed X inactivation, and single gene disorders or mutations. Among parents who suffer RPL, the best studied genetic cause is balanced chromosomal translocations. For evaluation of genetic abnormalities in cases of pregnancy loss, chromosomal microarray is more likely to yield interpretable results than karyotype due to cell culture failure. For parents, karyotype remains the standard since microarray may not detect truly balanced translocations. For those with an identified underlying genetic abnormality, preimplantation genetic testing has been proposed to optimize the live birth rate. This approach shows promise, but currently lacks supporting evidence. In summary, various genetic causes for recurrent pregnancy loss are known, but when such a cause is identified, the implications for management remain unclear.
Topics: Abortion, Habitual; Chromosome Aberrations; Female; Genetic Counseling; Humans; Karyotyping; Pregnancy; Translocation, Genetic
PubMed: 30638594
DOI: 10.1053/j.semperi.2018.12.002 -
PloS One 2014DNA methyltransferase 3A (DNMT3A) mutations were considered to be independently associated with unfavorable prognosis in adults with de novo acute myeloid leukemia... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
DNA methyltransferase 3A (DNMT3A) mutations were considered to be independently associated with unfavorable prognosis in adults with de novo acute myeloid leukemia (AML), however, there are still debates on this topic. Here, we aim to further investigate the association between DNMT3A mutations and prognosis of patients with AML.
METHODS
Eligible studies were identified from several data bases including PubMed, Embase, Web of Science, ClinicalTrials and the Cochrane Library (up to June 2013). The primary endpoint was overall survival (OS), while relapse-free survival (RFS) and event-free survival (EFS) were chosen as secondary endpoints. If possible, we would pool estimate effects (hazard ratio [HR] with 95% confidence interval[CI]) of outcomes in random and fixed effects models respectively.
RESULTS
That twelve cohort studies with 6377 patients exploring the potential significance of DNMT3A mutations on prognosis were included. Patients with DNMT3A mutations had slightly shorter OS (HR = 1.60; 95% CI, 1.31-1.95; P<0.001), as compared to wild-type carriers. Among the patients younger than 60 years of age, DNMT3A mutations predicted a worse OS (HR = 1.84; 95% CI, 1.36-2.50; P<0.001). In addition, mutant DNMT3A predicted inferior OS (HR = 2.30; 95% CI, 1.78-2.97; P = 0.862) in patients with unfavorable genotype abnormalities. Similar results were also found in some other subgroups. However, no significant prognostic value was found on OS (HR = 1.40; 95% CI, 0.98-1.99; P = 0.798) in the favorable genotype subgroup. Similar results were found on RFS and EFS under different conditions.
CONCLUSIONS
DNMT3A mutations have slightly but significantly poor prognostic impact on OS, RFS and EFS of adults with de novo AML in total population and some specific subgroups.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; DNA (Cytosine-5-)-Methyltransferases; DNA Methyltransferase 3A; Disease-Free Survival; Humans; Leukemia, Myeloid, Acute; Middle Aged; Mutation; Prognosis; Recurrence; Young Adult
PubMed: 24936645
DOI: 10.1371/journal.pone.0093353 -
Neuroepidemiology 2022Myotonic dystrophy (DM), the most common muscular dystrophy in adults, is a group of autosomal inherited neuromuscular disorders characterized by progressive muscle... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Myotonic dystrophy (DM), the most common muscular dystrophy in adults, is a group of autosomal inherited neuromuscular disorders characterized by progressive muscle weakness, myotonia, and cardiac conduction abnormalities. Due to the different gene mutations, DM has been subclassified into DM type 1 (DM1) and type 2 (DM2). However, the prevalence studies on DM and its subtypes are insufficient.
METHODS
The PubMed (1966-2022), MEDLINE (1950-2022), Web of Science (1864-2022), and Cochrane Library (2022) databases were searched for original research articles published in English. The quality of the included studies was assessed by a checklist adapted from Strengthening the Reporting of Observational studies in Epidemiology. To derive the pooled epidemiological prevalence estimates, a meta-analysis was performed using the random-effects model. Heterogeneity was assessed using the Cochrane Q statistic and the I2 statistic.
RESULTS
A total of 17 studies were included in the systematic review and meta-analysis. Of the 17 studies evaluated, 14 studies were considered medium quality, 2 studies were considered high quality, and 1 study was considered low quality. The global prevalence of DM varied widely from 0.37 to 36.29 cases per 100,000. The pooled estimate of the prevalence of DM was 9.99 cases (95% CI: 5.62-15.53) per 100,000. The pooled estimate of the prevalence of DM1 was 9.27 cases (95% CI: 4.73-15.21) per 100,000, ranging from 0.37 to 36.29 cases per 100,000. The pooled estimate of the prevalence of DM2 was 2.29 cases (95% CI: 0.17-6.53) per 100,000, ranging from 0.00 to 24.00 cases per 100,000.
CONCLUSION
Our study provided accurate estimates of the prevalence of DM. The high heterogeneity and the lack of high-quality studies highlight the need to conduct higher quality studies on orphan diseases.
Topics: Adult; Humans; Myotonic Dystrophy; Prevalence
PubMed: 35483324
DOI: 10.1159/000524734