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Journal of Biomedical Science Jun 2020Pulmonary diseases due to mycobacteria cause significant morbidity and mortality to human health. In addition to tuberculosis (TB), caused by Mycobacterium tuberculosis... (Review)
Review
Pulmonary diseases due to mycobacteria cause significant morbidity and mortality to human health. In addition to tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), recent epidemiological studies have shown the emergence of non-tuberculous mycobacteria (NTM) species in causing lung diseases in humans. Although more than 170 NTM species are present in various environmental niches, only a handful, primarily Mycobacterium avium complex and M. abscessus, have been implicated in pulmonary disease. While TB is transmitted through inhalation of aerosol droplets containing Mtb, generated by patients with symptomatic disease, NTM disease is mostly disseminated through aerosols originated from the environment. However, following inhalation, both Mtb and NTM are phagocytosed by alveolar macrophages in the lungs. Subsequently, various immune cells are recruited from the circulation to the site of infection, which leads to granuloma formation. Although the pathophysiology of TB and NTM diseases share several fundamental cellular and molecular events, the host-susceptibility to Mtb and NTM infections are different. Striking differences also exist in the disease presentation between TB and NTM cases. While NTM disease is primarily associated with bronchiectasis, this condition is rarely a predisposing factor for TB. Similarly, in Human Immunodeficiency Virus (HIV)-infected individuals, NTM disease presents as disseminated, extrapulmonary form rather than as a miliary, pulmonary disease, which is seen in Mtb infection. The diagnostic modalities for TB, including molecular diagnosis and drug-susceptibility testing (DST), are more advanced and possess a higher rate of sensitivity and specificity, compared to the tools available for NTM infections. In general, drug-sensitive TB is effectively treated with a standard multi-drug regimen containing well-defined first- and second-line antibiotics. However, the treatment of drug-resistant TB requires the additional, newer class of antibiotics in combination with or without the first and second-line drugs. In contrast, the NTM species display significant heterogeneity in their susceptibility to standard anti-TB drugs. Thus, the treatment for NTM diseases usually involves the use of macrolides and injectable aminoglycosides. Although well-established international guidelines are available, treatment of NTM disease is mostly empirical and not entirely successful. In general, the treatment duration is much longer for NTM diseases, compared to TB, and resection surgery of affected organ(s) is part of treatment for patients with NTM diseases that do not respond to the antibiotics treatment. Here, we discuss the epidemiology, diagnosis, and treatment modalities available for TB and NTM diseases of humans.
Topics: Female; Humans; Male; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Tuberculosis
PubMed: 32552732
DOI: 10.1186/s12929-020-00667-6 -
Molecular Diagnosis and Genetic Counseling of Cystic Fibrosis and Related Disorders: New Challenges.Genes Jun 2020Identification of the cystic fibrosis transmembrane conductance regulator gene and its numerous variants opened the way to fantastic breakthroughs in diagnosis,... (Review)
Review
Identification of the cystic fibrosis transmembrane conductance regulator gene and its numerous variants opened the way to fantastic breakthroughs in diagnosis, research and treatment of cystic fibrosis (CF). The current and future challenges of molecular diagnosis of CF and CFTR-related disorders and of genetic counseling are here reviewed. Technological advances have enabled to make a diagnosis of CF with a sensitivity of 99% by using next generation sequencing in a single step. The detection of heretofore unidentified variants and ethnic-specific variants remains challenging, especially for newborn screening (NBS), CF carrier testing and genotype-guided therapy. Among the criteria for assessing the impact of variants, population genetics data are insufficiently taken into account and the penetrance of CF associated with variants remains poorly known. The huge diversity of diagnostic and genetic counseling indications for studies makes assessment of variant disease-liability critical. This is especially discussed in the perspective of wide genome analyses for NBS and CF carrier screening in the general population, as future challenges.
Topics: Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Genetic Counseling; Genotype; Humans; Infant, Newborn; Neonatal Screening; Pathology, Molecular; Penetrance
PubMed: 32512765
DOI: 10.3390/genes11060619 -
Frontiers in Pediatrics 2019Beckwith-Wiedemann syndrome (BWS) is a human genomic imprinting disorder that presents with a wide spectrum of clinical features including overgrowth, abdominal wall... (Review)
Review
Beckwith-Wiedemann syndrome (BWS) is a human genomic imprinting disorder that presents with a wide spectrum of clinical features including overgrowth, abdominal wall defects, macroglossia, neonatal hypoglycemia, and predisposition to embryonal tumors. It is associated with genetic and epigenetic changes on the chromosome 11p15 region, which includes two imprinting control regions. Here we review strategies for diagnosing and managing BWS and delineate commonly used genetic tests to establish a molecular diagnosis of BWS. Recommended first-line testing assesses DNA methylation and copy number variation of the BWS region. Tissue mosaicism can occur in patients with BWS, posing a challenge for genetic testing, and a negative test result does not exclude a diagnosis of BWS. Further testing should analyze additional tissue samples or employ techniques with higher diagnostic yield. Identifying the BWS molecular subtype is valuable for coordinating patient care because of the (epi)genotype-phenotype correlations, including different risks and types of embryonal tumors.
PubMed: 32039119
DOI: 10.3389/fped.2019.00562 -
Journal of Mother and Child Mar 2022Joubert syndrome (JS; MIM PS213300) is a rare genetic autosomal recessive disease characterized by cerebellar vermis hypoplasia, a distinctive malformation of the... (Review)
Review
Joubert syndrome (JS; MIM PS213300) is a rare genetic autosomal recessive disease characterized by cerebellar vermis hypoplasia, a distinctive malformation of the cerebellum and the so-called "molar tooth sign." Other characteristic features are hypotonia with lateral ataxia, intellectual disability/mental retardation, oculomotor apraxia, retinal dystrophy, abnormalities in the respiratory system, renal cysts, hepatic fibrosis, and skeletal changes. Such pleiotropic characteristics are typical of many disorders involving primary cilium aberrations, providing a significant overlap between JS and other ciliopathies such as nephronophthisis, Meckel syndrome, and Bardet-Biedl syndrome. This review will describe some characteristics of JS associated with changes in 35 genes, and will also address subtypes of JS, clinical diagnosis, and the future of therapeutic developments.
Topics: Humans; Cerebellum; Abnormalities, Multiple; Eye Abnormalities; Retina; Polycystic Kidney Diseases; Intellectual Disability
PubMed: 36803942
DOI: 10.34763/jmotherandchild.20222601.d-22-00034 -
American Journal of Clinical Pathology Jun 2021Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma derived from T-follicular helper cells. For pathologists, diagnosing AITL may be... (Review)
Review
OBJECTIVES
Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma derived from T-follicular helper cells. For pathologists, diagnosing AITL may be challenging due to its wide clinical and histopathologic spectrum, which can mimic a variety of reactive and neoplastic processes.
METHODS
We summarize and discuss the clinicopathologic features of AITL, emphasizing diagnostic tools available to the practicing pathologist. Common diagnostic dilemmas are discussed.
RESULTS
AITL exhibits various histologic patterns and is often associated with a prominent microenvironment that can obscure the neoplastic cells. Atypical B-cell proliferations, which can take a number of forms, are common in AITL, and clonal B-cell expansion can be seen. The atypical B cells can closely resemble Hodgkin/Reed-Sternberg cells, leading to misdiagnosis as classic Hodgkin lymphoma. Molecular studies have revealed recurrent genetic alterations, which can aid in differential diagnosis, particularly in problematic cases.
CONCLUSIONS
Given the complex diagnostic challenges in AITL, an integrated approach, incorporating clinical, morphologic, immunophenotypic, and molecular findings, is helpful to reach an accurate diagnosis.
Topics: Humans; Immunoblastic Lymphadenopathy; Lymphoma, T-Cell, Peripheral
PubMed: 34117736
DOI: 10.1093/ajcp/aqab090 -
World Journal of Hepatology Nov 2022Haemochromatosis is a genetic disease caused by hepcidin deficiency, responsible for an increase in intestinal iron absorption. Haemochromatosis is associated with... (Review)
Review
Haemochromatosis is a genetic disease caused by hepcidin deficiency, responsible for an increase in intestinal iron absorption. Haemochromatosis is associated with homozygosity for the p.Cys282Tyr mutation. However, rare cases of haemochromatosis (non- haemochromatosis) can also be caused by pathogenic variants in other genes (such as , and ). A working group of the International Society for the Study of Iron in Biology and Medicine (BIOIRON Society) has concluded that the classification based in different molecular subtypes is difficult to be adopted in clinical practice and has proposed a new classification approaching clinical questions and molecular complexity. The aim of the present review is to provide an update on classification, pathophysiology and therapeutic recommendations.
PubMed: 36483608
DOI: 10.4254/wjh.v14.i11.1931 -
International Journal of Laboratory... Sep 2022Hemoglobinopathies are the most common monogenic disorders in the world with an ever increasing global disease burden each year. As most hemoglobinopathies show... (Review)
Review
Hemoglobinopathies are the most common monogenic disorders in the world with an ever increasing global disease burden each year. As most hemoglobinopathies show recessive inheritance carriers are usually clinically silent. Programmes for preconception and antenatal carrier screening, with the option of prenatal diagnosis are considered beneficial in many endemic countries. With the development of genetic tools such as Array analysis and Next Generation Sequencing in addition to state of the art screening at the hematologic, biochemic and genetic level, have contributed to the discovery of an increasing number of rare rearrangements and novel factors influencing the disease severity over the recent years. This review summarizes the basic requirements for adequate carrier screening analysis, the importance of genotype-phenotype correlation and how this may lead to the unrevealing exceptional interactions causing a clinically more severe phenotype in otherwise asymptomatic carriers. A special group of patients are β-thalassemia carriers presenting with features of β-thalassemia intermedia of various clinical severity. The disease mechanisms may involve duplicated α-globin genes, mosaic partial Uniparental Isodisomy of chromosome 11p15.4 where the HBB gene is located or haplo-insufficiency of a non-linked gene SUPT5H on chromosome 19q, first described in two Dutch families with β-thalassemia trait without variants in the HBB gene.
Topics: Female; Genotype; Hemoglobinopathies; Humans; Nuclear Proteins; Phenotype; Pregnancy; Prenatal Diagnosis; Transcriptional Elongation Factors; alpha-Globins; beta-Thalassemia
PubMed: 36074711
DOI: 10.1111/ijlh.13885 -
Biosensors Oct 2022For the identification of nucleic acids, which are important biomarkers of pathogen-mediated diseases and viruses, the gold standard for NA-based diagnostic applications... (Review)
Review
For the identification of nucleic acids, which are important biomarkers of pathogen-mediated diseases and viruses, the gold standard for NA-based diagnostic applications is polymerase chain reaction (PCR). However, the requirements of PCR limit its application as a rapid point-of-care diagnostic technique. To address the challenges associated with regular PCR, many isothermal amplification methods have been developed to accurately detect NAs. Isothermal amplification methods enable NA amplification without changes in temperature with simple devices, as well as faster amplification times compared with regular PCR. Of the isothermal amplifications, loop-mediated isothermal amplification (LAMP) is the most studied because it amplifies NAs rapidly and specifically. This review describes the principles of LAMP, the methods used to monitor the process of LAMP, and examples of biosensors that detect the amplicons of LAMP. In addition, current trends in the application of LAMP to smartphones and self-diagnosis systems for point-of-care tests are also discussed.
Topics: Sensitivity and Specificity; Nucleic Acid Amplification Techniques; Nucleic Acids; Point-of-Care Testing
PubMed: 36290994
DOI: 10.3390/bios12100857 -
International Journal of Molecular... Mar 2023Soft tissue tumors are rare mesenchymal tumors with divergent differentiation. The diagnosis of soft tissue tumors is challenging for pathologists owing to the diversity... (Review)
Review
Soft tissue tumors are rare mesenchymal tumors with divergent differentiation. The diagnosis of soft tissue tumors is challenging for pathologists owing to the diversity of tumor types and histological overlap among the tumor entities. Present-day understanding of the molecular pathogenesis of soft tissue tumors has rapidly increased with the development of molecular genetic techniques (e.g., next-generation sequencing). Additionally, immunohistochemical markers that serve as surrogate markers for recurrent translocations in soft tissue tumors have been developed. This review aims to provide an update on recently described molecular findings and relevant novel immunohistochemical markers in selected soft tissue tumors.
Topics: Humans; Sarcoma; Translocation, Genetic; In Situ Hybridization, Fluorescence; Diagnosis, Differential; Soft Tissue Neoplasms; Biomarkers, Tumor
PubMed: 36983010
DOI: 10.3390/ijms24065934 -
Molecular Genetics & Genomic Medicine Jul 2020Anorexia nervosa is a multifactorial eating disorder that manifests with self-starvation, extreme anxiety, hyperactivity, and amenorrhea. Long-term effects include organ... (Review)
Review
BACKGROUND
Anorexia nervosa is a multifactorial eating disorder that manifests with self-starvation, extreme anxiety, hyperactivity, and amenorrhea. Long-term effects include organ failure, disability, and in extreme cases, even death.
METHODS
Through a literature search, here we summarize what is known about the molecular etiology of anorexia nervosa and propose genetic testing for this condition.
RESULTS
Anorexia nervosa often has a familial background and shows strong heritability. Various genetic studies along with genome-wide association studies have identified several genetic loci involved in molecular pathways that might lead to anorexia.
CONCLUSION
Anorexia nervosa is an eating disorder with a strong genetic component that contributes to its etiology. Various genetic approaches might help in the molecular diagnosis of this disease and in devising novel therapeutic options.
Topics: Animals; Anorexia Nervosa; Genetic Predisposition to Disease; Genetic Testing; Humans; Molecular Targeted Therapy
PubMed: 32368866
DOI: 10.1002/mgg3.1244