Hereditary Disease

Hereditary kidney diseases are common causes of chronic kidney disease (CKD) in children and adolescents, and also has an important role in the onset and progression of CKD in adulthood. Constructing a data sharing registration system for hereditary kidney disease and forming representative data with Chinese population specificity, is of great significance for achieving phenotype and genotype characterization, improving precision management level and mechanism research. The high heterogeneity of the disease and the scattered distribution of patients have led to a lack of understanding and unified management standards for hereditary kidney disease...

Leber's hereditary optic atrophy (LHON) is a genetic optic neuropathy that is more prevalent in young males but can occur from childhood to old age. The primary cause is mitochondrial genetic mutations, which are associated with dysfunction of mitochondrial electron transport chain complex I. It manifests as acute to subacute visual impairment, often starting unilaterally but progressing to involve both eyes within weeks to months. Visual loss is severe, with many patients having corrected visual acuity below 0...

Delivering functional gene into targeted skin cells or tissues to modulate the genes expression, has the potential to treat various hereditary cutaneous disorders. Nevertheless, the lack of safe and effective gene delivery vehicles greatly limits the clinical translation of gene therapy for inherited skin diseases. Herein, we developed a facile elution fractionation strategy to isolate eight HPAEs with Mw ranging from 7.6 to 131.8 kg/mol and Đ < 2.0 from the one crude HPAE23.7k , and investigated the expression efficiency for TGM1 and COL7A1 plasmids...

Activation of autophagy, a process of cellular stress response, leads to the breakdown of proteins, organelles, and other parts of the cell in lysosomes, and can be linked to several ailments, such as cancer, neurological diseases, and rare hereditary syndromes. Thus, its regulation is very carefully monitored. Transcriptional and post-translational mechanisms domestically or in whole organisms utilized to control the autophagic activity, have been heavily researched. In modern times, microRNAs (miRNAs) are being considered to have a part in post-translational orchestration of the autophagic activity, with miR-21 as one of the best studied miRNAs, it is often more than expressed in cancer cells...

Hereditary hypophosphatemic rickets with hypercalciuria is an autosomal recessive phosphate-wasting disorder, associated with kidney and skeletal pathologies, which is caused by pathogenic variants of SLC34A3. In this issue, Zhu et al. describe a pooled analysis of 304 individuals carrying SLC34A3 variants. Their study underscores the complexity of hereditary hypophosphatemic rickets with hypercalciuria, as kidney and bone phenotypes generally do not coexist, heterozygous carriers of SLC34A3 variants also can be affected, and the response to oral phosphate supplementation is dependent on the genetic status...

Hereditary breast and ovarian cancer syndrome is an autosomal dominant cancer susceptibility syndrome mainly due to variants in BRCA1 or BRCA2 genes. Patients presenting with BRCA1 or BRCA2 gene mutations have a lifetime risk of developing breast or ovarian cancer (80% and 40%, respectively). Genetic testing to explore the predisposition to develop cancer represents a pivotal factor in such cases, and this review wants to explore the main implications in terms of medicolegal liability and insurance issues. Medicolegal issues related to these diagnostic processes include: (a) failure to recommend the test; (b) failure to properly interpret the test; (c) failure to correctly translate results into clinical practice; (d) lack of informed consent; and (e) failure to refer patients to specialized genetic counseling...

BACKGROUND: Acute hepatic porphyrias (AHPs) are a group of rare diseases that encompasses acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and 5-aminolaevulinic acid dehydratase deficiency porphyria. Symptoms of AHP are nonspecific which, together with its low prevalence, difficult the diagnosis and follow-up of these patients. MATERIAL AND METHODS: This project used DELPHI methodology to answer PICO questions related to management of patients with AHPs...

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Systemic lupus erythematosus (SLE) and other autoimmune diseases are thought to develop in genetically predisposed individuals when triggered by environmental factors. This paradigm does not fully explain disease development, as it fails to consider the delay between birth and disease expression. In this review, we discuss observations described in T cells from patients with SLE that are not related to hereditary factors and have therefore been considered secondary to the disease process itself. Here, we contextualize some of those observations and argue that they may represent a pathogenic layer between genetic factors and disease development...

INTRODUCTION: Generalized joint hypermobility (GJH) can be the result of several hereditary connective tissue disorders, especially Ehlers-Danlos syndrome. Cerebrovascular manifestations are among the most common complications in this disorder, and understanding their extent can help better diagnosis and prevention of hazardous events. We investigated visual evoked potential (VEP) changes in patients with GJH and compared them with healthy individuals. METHODS: Our case-control study included 90 patients who fulfilled the Beighton score (B score) for joint hypermobility and other 90 healthy participants...

We review the evidence for the presence of stem/progenitor cells in the heart and the preclinical and clinical data using diverse cell types for the therapy of cardiac diseases. We highlight the failure of adult stem/progenitor cells to ameliorate heart function in most cardiac diseases, with the possible exception of refractory angina. The use of pluripotent stem cell-derived cardiomyocytes is analysed as a viable alternative therapeutic option but still needs further research at preclinical and clinical stages...

Sickle cell disease (SCD) is a hereditary hemoglobinopathy marked by hemolytic anemia and vaso-occlusive events (VOE). Chronic endothelial activation, inflammation, and coagulation activation contribute to vascular congestion, VOE, and end-organ damage. Coagulation proteases like thrombin and activated protein C (APC) modulate inflammation and endothelial dysfunction by activating protease-activated receptor 1 (PAR1), a G-protein coupled receptor. Thrombin cleaves PAR1 at Arg41, while APC cleaves PAR1 at Arg46, initiating either pro-inflammatory or cytoprotective signaling, respectively, a signaling conundrum known as biased agonism...

Polyneuropathy is a disease of the peripheral nervous system that usually results in distally emphasized, often symmetrical sensory and motor stimulation and deficits. These are often extremely painful. They can be divided into hereditary and acquired causes; inflammatory and infectious causes should be further differentiated among the acquired causes. A careful diagnostic workup is essential. Clinical signs and distribution patterns of symptoms can often already provide clues to the underlying aetiology...

Digital precision medicine is gaining increasing importance in rhythmology, especially in the treatment of cardiac arrhythmias. This trend is driven by the advancing digitization in healthcare and the availability of large amounts of data from various sources such as electrocardiograms (ECGs), implants like pacemakers and implantable cardioverter-defibrillators (ICDs), as well as wearables like smartwatches and fitness trackers. Through the analysis of this data, physicians can develop more precise and individualized diagnoses and treatment strategies for patients with cardiac arrhythmias...

Autonomic nervous system (ANS) regulation in hereditary angioedema (HAE) and coronavirus disease 2019 (COVID-19) is unknown. ANS alterations could be manifested during both the acute and post-acute phases of COVID-19. Implications of acute and chronic inflammation on ANS in HAE need to be addressed. In this case report, we monitored the systolic arterial blood pressure variability and baroreflex sensitivity in a female HAE patient both before experiencing COVID-19 symptoms and one month afterward. We also tracked the heart rate variability on the day preceding symptom onset, the day of symptom onset (SYM), the day following SYM, five days after SYM, the day of the first negative nasopharyngeal swab (i...

BACKGROUND: Friedreich's ataxia (FRDA) is a rare hereditary neurodegenerative disorder characterized by progressive ataxia, cardiomyopathy, and diabetes. The disease is caused by a deficiency of frataxin, a mitochondrial protein involved in iron-sulfur cluster synthesis and iron metabolism. OBJECTIVE: This review aims to summarize recent advances in the development of treatment strategies for FRDA, with a focus on potential drug candidates and their mechanisms of action...

BACKGROUND: Primary lymphedema is the most common form of lymphedema presenting in the pediatric age group. Childhood lymphedema is caused by hereditary or congenital malformations in the lymphatic system that can manifest at birth or during childhood or adolescence. OBJECTIVES: Complex decongestive therapy (CDT) is the cornerstone of conservative management of lymphedema in both adult and pediatric lymphedema patients, although pediatric treatment guidelines are still lacking...

BACKGROUND: Familial primary hyperparathyroidism (PHPT) includes syndromic and non-syndromic disorders. The former are characterized by the occurrence of PHPT in association with extra-parathyroid manifestations and includes multiple endocrine neoplasia (MEN) types 1, 2, and 4 syndromes, and hyperparathyroidism-jaw tumor (HPT-JT). The latter consists of familial hypocalciuric hypercalcemia (FHH) types 1, 2 and 3, neonatal severe primary hyperparathyroidism (NSHPT), and familial isolated primary hyperparathyroidism (FIHP)...

A 35-year-old woman of Asian descent with epigastralgia was referred to our hospital. Esophagogastroduodenoscopy revealed gastric cancer in the upper body and carpeting fundic gland polyposis in the fornix and body. Computed tomography revealed no metastases. Total colonoscopy and capsule endoscopy revealed no polyposis, except in the stomach. The patient was diagnosed with advanced gastric cancer and underwent open total gastrectomy. We speculated that her gastric cancer was a hereditary tumor due to its early onset and accompanying fundic gland polyposis...

Deep learning models for variant pathogenicity prediction can recapitulate expert-curated annotations, but their performance remains unexplored on actual disease phenotypes in a real-world setting. Here, we apply three state-of-the-art pathogenicity prediction models to classify hereditary breast cancer gene variants in the UK Biobank. Predicted pathogenic variants in BRCA1, BRCA2 and PALB2 , but not ATM and CHEK2 , were associated with increased breast cancer risk. We explored gene-specific score thresholds for variant pathogenicity, finding that they could improve model performance...