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Journal of Clinical Medicine Mar 2021Left ventricular noncompaction (LVNC) is a heterogeneous, often hereditary group of diseases, which may have diverse clinical manifestations. This article reviews the... (Review)
Review
Left ventricular noncompaction (LVNC) is a heterogeneous, often hereditary group of diseases, which may have diverse clinical manifestations. This article reviews the risk factors for unfavorable outcomes of LVNC in children, as well as discuss the diagnostic methods and the differences between pediatric and adult LVNC. Through a systematic review of the literature, a total of 1983 articles were outlined; 23 of them met the inclusion criteria. In echocardiography the following have been associated with adverse outcomes in children: Left ventricular ejection fraction, end-diastolic dimension, left ventricular posterior wall compaction, and decreased strains. T-wave abnormalities and increased spatial peak QRS-T angle in ECG, as well as arrhythmia, were observed in children at greater risk. Cardiac magnetic resonance is a valuable tool to identify those with systolic dysfunction and late gadolinium enhancement. Genetic testing appears to help identify children at risk, because mutations in particular genes have been associated with worse outcomes. ECG and imaging tests, such as echocardiography and magnetic resonance, help outline risk factors for unfavorable outcomes of LVNC in children and in identifying outpatients who require more attention. Refining the current diagnostic criteria is crucial to avoid inadequate restrain from physical activity.
PubMed: 33809657
DOI: 10.3390/jcm10061232 -
Current Rheumatology Reports May 2020Lupus erythematosus (LE) is characterized by broad and varied clinical forms ranging from a localized skin lesion to a life-threatening form with severe systemic...
PURPOSE OF REVIEW
Lupus erythematosus (LE) is characterized by broad and varied clinical forms ranging from a localized skin lesion to a life-threatening form with severe systemic manifestations. The overlapping between cutaneous LE (CLE) and systemic LE (SLE) brings difficulties to physicians for early accurate diagnosis and sometimes may lead to delayed treatment for patients. We comprehensively review recent progress about the similarities and differences of the main three subsets of LE in pathogenesis and immunological mechanisms, with a particular focus on the skin damage.
RECENT FINDINGS
Recent studies on the mechanisms contributing to the skin damage in lupus have shown a close association of abnormal circulating inflammatory cells and abundant production of IgG autoantibodies with the skin damage of SLE, whereas few evidences if serum autoantibodies and circulating inflammatory cells are involved in the pathogenesis of CLE, especially for the discoid LE (DLE). Till now, the pathogenesis and molecular/cellular mechanism for the progress from CLE to SLE are far from clear. But more and more factors correlated with the differences among the subsets of LE and progression from CLE to SLE have been found, such as the mutation of IRF5, IFN regulatory factors and abnormalities of plasmacytoid dendritic cells (PDCs), Th1 cells, and B cells, which could be the potential biomarkers for the interventions in the development of LE. A further understanding in pathogenesis and immunological mechanisms for skin damage in different subsets of LE makes us think more about the differences and cross-links in the pathogenic mechanism of CLE and SLE, which will shed a light in predictive biomarkers and therapies in LE.
Topics: Acute Disease; Disease Progression; Humans; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic; Microbiota; Skin; Ultraviolet Rays
PubMed: 32399815
DOI: 10.1007/s11926-020-00893-9 -
Pathology Oncology Research : POR Jul 2020We aimed to classify undifferentiated/dedifferentiated carcinoma (UDC/DDC) according to the four TCGA molecular subgroups of endometrial cancer:... (Meta-Analysis)
Meta-Analysis
We aimed to classify undifferentiated/dedifferentiated carcinoma (UDC/DDC) according to the four TCGA molecular subgroups of endometrial cancer: microsatellite-instable/hypermutated (MSI), POLE-mutant/ultramutated (POLE), copy-number-low/p53-wild-type (p53wt), and copy-number-high/p53-abnormal (p53abn), through a systematic review and meta-analysis. Electronic databases were searched from January 2013 to July 2019 for studies assessing the TCGA classification in endometrial UDC/DDC series. Pooled prevalence of each TCGA subgroup on the total UDC/DDCs was calculated. Three studies with 73 patients were included. Pooled prevalence of the TCGA subgroups were: 12.4% for the POLE subgroup, 44% for the MSI subgroup, 18.6% for the p53abn subgroup, 25% for the p53wt group. All TCGA groups are represented in UDC/DDC, with a predominance of the MSI group, indicating a biological heterogeneity. Hypermutated/ultramutated cancers constitute the majority of UDC/DDC, suggesting a crucial difference with other high-risk histologies of endometrial carcinoma.
Topics: Endometrial Neoplasms; Female; Gene Dosage; Humans; Mutation; Transcriptome
PubMed: 31811476
DOI: 10.1007/s12253-019-00784-0 -
Neurology Nov 2022There is accumulating evidence in the literature indicating a strong correlation between Fabry disease (FD) phenotypes and specific sequence variations in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
There is accumulating evidence in the literature indicating a strong correlation between Fabry disease (FD) phenotypes and specific sequence variations in the Galactosidase Alpha () gene. Among them, the potential pathogenicity and clinical relevance of variation in patients with FD remain debated.
METHODS
We performed a systematic review and meta-analysis of studies reporting as single occurring variant in the gene and sought to evaluate (1) the prevalence of variation in different populations with or without clinical manifestations of FD, (2) the clinical FD phenotype in -positive patients, and (3) the proportion of -positive patients presenting abnormal laboratory findings (alpha-galactosidase-A deficiency or globotriaosylceramide accumulation).
RESULTS
Forty cohorts comprising 211 individuals with variation among 42,723 participants with available gene-sequencing data were included. Patients highly suspected for FD had a higher prevalence of variation (4.9%, 95% CI 1.6%-9.9%; I = 95.5%) compared with the general population (0%, 95% CI 0%-0.1%; I = 1.9%; = 0.004). The prevalence of variation was 0.6% (95% CI 0.3%-1%; I = 74.1%), 0.4% (95% CI 0.2%-0.7%; I = 0%), and 0.3% (95% CI 0.2%-0.4%; I = 0%) in patients presenting with neurologic, cardiac, or renal manifestations, respectively. was associated with a milder, late-onset FD phenotype, as indicated by the mean patient age of 51 years (95% CI 44-59; I = 94%) and the evidence of alpha-galactosidase A deficiency and globotriaosylceramide accumulation in 26.7% (95% CI 15.3%-40%; I = 34%) and 16.2% (95% CI 8%-26.4%; I = 35%) of cases, respectively. -positive patients displayed predominantly neurologic FD manifestations (58.1%, 95% CI 37.7%-77.1%; I = 78%), with central and peripheral nervous system (CNS/PNS) involvement noted in 28.2% (95% CI 15.4%-43.2%; I = 51%) and 28.5% (95% CI 17.8%-40.5%; I = 61%) of cases, respectively.
DISCUSSION
variation seems to correlate with an atypical, mild late-onset phenotype with predominantly neurologic FD manifestations. Monitoring for CNS/PNS involvement is thus paramount to identify -positive patients with latent or early-FD pathology, which may qualify for enzyme-replacement therapy or chaperone treatment.
Topics: Humans; Fabry Disease; alpha-Galactosidase; Mutation; Trihexosylceramides
PubMed: 36344272
DOI: 10.1212/WNL.0000000000201102 -
Frontiers in Medicine 2021Keratoconus (KC) is an etiologically heterogeneous corneal ectatic disorder. To systematically display the pathogenesis of keratoconus (KC), this study reviewed all the...
Keratoconus (KC) is an etiologically heterogeneous corneal ectatic disorder. To systematically display the pathogenesis of keratoconus (KC), this study reviewed all the reported genes involved in KC, and performed an enrichment analysis of genes identified at the genome, transcription, and protein levels respectively. Combined analysis of multi-level results revealed their shared genes, gene ontology (GO), and pathway terms, to explore the possible pathogenesis of KC. After an initial search, 80 candidate genes, 2,933 transcriptional differential genes, and 947 differential proteins were collected. The candidate genes were significantly enriched in extracellular matrix (ECM) related terms, Wnt signaling pathway and cytokine activities. The enriched GO/pathway terms of transcription and protein levels highlight the importance of ECM, cell adhesion, and inflammatory once again. Combined analysis of multi-levels identified 13 genes, 43 GOs, and 12 pathways. The pathogenic relationships among these overlapping factors maybe as follows. The gene mutations/variants caused insufficient protein dosage or abnormal function, together with environmental stimulation, leading to the related functions and pathways changes in the corneal cells. These included response to the glucocorticoid and reactive oxygen species; regulation of various signaling (P13K-AKT, MAPK and NF-kappaB), apoptosis and aging; upregulation of cytokines and collagen-related enzymes; and downregulation of collagen and other ECM-related proteins. These undoubtedly lead to a reduction of extracellular components and induction of cell apoptosis, resulting in the loosening and thinning of corneal tissue structure. This study, in addition to providing information about the genes involved, also provides an integrated insight into the gene-based etiology and pathogenesis of KC.
PubMed: 35141241
DOI: 10.3389/fmed.2021.770138 -
International Journal of Dermatology Mar 2021Hidradenitis suppurativa (HS) is a chronic inflammatory follicular disorder that involves painful nodules, abscesses, and tunnels of intertriginous sites. Although the... (Review)
Review
Hidradenitis suppurativa (HS) is a chronic inflammatory follicular disorder that involves painful nodules, abscesses, and tunnels of intertriginous sites. Although the etiology has not been fully elucidated, recent studies have highlighted its association with chromosomal abnormalities.We present a rare case of HS in a patient with Trisomy 1q;13 and systematically summarize the association between HS and chromosomal abnormalities. A search was conducted using MEDLINE and EMBASE in OVID database. Original studies reporting HS among human subjects with chromosomal abnormalities were included. Patient demographics, disease symptomology, clinical features, and treatment histories were extracted and summarized.Thirteen studies describing 428 cases met the inclusion criteria. Of the 13 articles, nine studies reported patients with HS and Down syndrome (DS), one article investigated HS and Smith-Magenis syndrome (SMS), and three articles analyzed HS and Patau syndrome (PS). While increased prevalence of HS was found in populations with DS, with suggested mechanisms involving amyloid precursor protein cleavage product, keratinocyte proliferation, and follicular plugging, the associations between HS and both SMS and PS remain inconclusive because of limited studies with small sample size.Although evidence suggests that the genetic regulation of chromosome 21 may be implicated in the association between HS and DS, this association may be confounded by additional factors that increase the risk of HS. Further research with larger sample sizes must be conducted to strengthen our understanding of the association between HS and chromosomal abnormalities.
Topics: Chromosome Aberrations; Down Syndrome; Hidradenitis Suppurativa; Humans; Prevalence
PubMed: 33599294
DOI: 10.1111/ijd.15111 -
Genes Jun 2022According to current estimates, infertility affects one in four couples trying to conceive. Primary or secondary infertility can be due either to both partners or only... (Review)
Review
According to current estimates, infertility affects one in four couples trying to conceive. Primary or secondary infertility can be due either to both partners or only to the man or the woman. Up to 15% of infertility cases in men can be attributed to genetic factors that can lead to irreversible partial or complete spermatogenic arrest. The increased use of assisted reproductive technology (ART) has provided not only insights into the causes of male infertility but also afforded a diagnostic tool to detect and manage this condition among couples. Genes control a variety of physiological attributes, such as the hypothalamic-pituitary-gonadal axis, development, and germ cell differentiation. In the era of ART, it is important to understand the genetic basis of infertility so as to provide the most tailored therapy and counseling to couples. Genetic factors involved in male infertility can be chromosome abnormalities or single-gene disorders, mitochondrial DNA (mtDNA) mutations, Y-chromosome deletions, multifactorial disorders, imprinting disorders, or endocrine disorders of genetic origin. In this review, we discuss the role of mitochondria and the mitochondrial genome as an indicator of sperm quality and fertility.
Topics: Azoospermia; DNA, Mitochondrial; Female; Humans; Infertility, Male; Male; Mitochondria; Reproductive Techniques, Assisted; Semen
PubMed: 35885965
DOI: 10.3390/genes13071182 -
Liver International : Official Journal... Mar 2024To systematically review the literature for reports on Wolcott-Rallison syndrome, focusing on the spectrum and natural history, genotype-phenotype correlations, patient...
BACKGROUND AND AIMS
To systematically review the literature for reports on Wolcott-Rallison syndrome, focusing on the spectrum and natural history, genotype-phenotype correlations, patient and native liver survival, and long-term outcomes.
METHODS
PubMed, Livio, Google Scholar, Scopus and Web of Science databases were searched. Data on genotype, phenotype, therapy, cause of death and follow-up were extracted. Survival and correlation analyses were performed.
RESULTS
Sixty-two studies with 159 patients met the inclusion criteria and additional 30 WRS individuals were collected by personal contact. The median age of presentation was 2.5 months (IQR 2) and of death was 36 months (IQR 50.75). The most frequent clinical feature was neonatal diabetes in all patients, followed by liver impairment in 73%, impaired growth in 72%, skeletal abnormalities in 59.8%, the nervous system in 37.6%, the kidney in 35.4%, insufficient haematopoiesis in 34.4%, hypothyroidism in 14.8% and exocrine pancreas insufficiency in 10.6%. Episodes of acute liver failure were frequently reported. Liver transplantation was performed in six, combined liver-pancreas in one and combined liver-pancreas-kidney transplantation in two individuals. Patient survival was significantly better in the transplant cohort (p = .0057). One-, five- and ten-year patient survival rates were 89.4%, 65.5% and 53.1%, respectively. Liver failure was reported as the leading cause of death in 17.9% of cases. Overall survival was better in individuals with missense mutations (p = .013).
CONCLUSION
Wolcott-Rallison syndrome has variable clinical courses. Overall survival is better in individuals with missense mutations. Liver- or multi-organ transplantation is a feasible treatment option to improve survival.
Topics: Infant, Newborn; Humans; Infant; Follow-Up Studies; Diabetes Mellitus, Type 1; Osteochondrodysplasias; Diabetes Mellitus; eIF-2 Kinase; Epiphyses
PubMed: 38230874
DOI: 10.1111/liv.15834 -
Cancers Jun 2022Despite the major advances in screening and therapeutic approaches, gynaecological malignancies still present as a leading cause of death among women of reproductive... (Review)
Review
Despite the major advances in screening and therapeutic approaches, gynaecological malignancies still present as a leading cause of death among women of reproductive age. Cervical cancer, although largely preventable through vaccination and regular screening, remains the fourth most common and most lethal cancer type in women, while the available treatment schemes still pose a fertility threat. Ovarian cancer is associated with high morbidity rates, primarily due to lack of symptoms and high relapse rates following treatment, whereas endometrial cancer, although usually curable by surgery, it still represents a therapeutic problem. On the other hand, benign abnormalities, such as fibroids, endometriosis, placental, and embryo implantation disorders, although not life-threatening, significantly affect women's life and fertility and have high socio-economic impacts. In the last decade, targeted gene therapy approaches toward both malignant and benign gynaecological abnormalities have led to promising results, setting the ground for successful clinical trials. The above therapeutic strategies employ both viral and non-viral systems for mutation compensation, suicide gene therapy, oncolytic virotherapy, antiangiogenesis and immunopotentiation. This review discusses all the major advances in gene therapy of gynaecological disorders and highlights the novel and potentially therapeutic perspectives associated with such an approach.
PubMed: 35805007
DOI: 10.3390/cancers14133238 -
Human Genetics Dec 2021ATR-X, an acronym for alpha thalassemia and mental retardation X-linked, syndrome is a congenital condition predominantly affecting males, characterized by mild to...
ATR-X, an acronym for alpha thalassemia and mental retardation X-linked, syndrome is a congenital condition predominantly affecting males, characterized by mild to severe intellectual disability, facial, skeletal, urogenital, and hematopoietic anomalies. Less common are heart defects, eye anomalies, renal abnormalities, and gastrointestinal dysfunction. ATR-X syndrome is caused by germline variants in the ATRX gene. Until recently, the diagnosis of the ATR-X syndrome had been guided by the classical clinical manifestations and confirmed by molecular techniques. However, our new systematic analysis shows that the only clinical sign shared by all affected individuals is intellectual disability, with the other manifestations varying even within the same family. More than 190 different germline ATRX mutations in some 200 patients have been analyzed. With improved and more frequent analysis by molecular technologies, more subtle deletions and insertions have been detected recently. Moreover, emerging technologies reveal non-classic phenotypes of ATR-X syndrome as well as the description of a new clinical feature, the development of osteosarcoma which suggests an increased cancer risk in ATR-X syndrome. This review will focus on the different types of inherited ATRX mutations and their relation to clinical features in the ATR-X syndrome. We will provide an update of the frequency of clinical manifestations, the affected organs, and the genotype-phenotype correlations. Finally, we propose a shift in the diagnosis of ATR-X patients, from a clinical diagnosis to a molecular-based approach. This may assist clinicians in patient management, risk assessment and genetic counseling.
Topics: Animals; Humans; Intellectual Disability; Mental Retardation, X-Linked; Molecular Diagnostic Techniques; Mutation; alpha-Thalassemia
PubMed: 34524523
DOI: 10.1007/s00439-021-02361-5