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Rare Monogenic Diseases
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Topic review
Updated time: 17 May 2021
Submitted by: Jean-Michel Rozet
Definition: Iris integrity is required to regulate both the amount of light reaching the retina and intraocular pressure (IOP), with elevated IOP being a major risk factor for glaucoma. Congenital microcoria (MCOR) is an extremely rare, autosomal dominant disease affecting iris development and hindering both of these functions.
Entry Collection : Rare Monogenic Diseases
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Topic review
Updated time: 24 Mar 2021
Submitted by: Daniela Sorriento
Definition: Fabry disease (FD) is a lysosomal storage disorder, depending on defects in alpha-galactosidase A (GAL) activity. At the clinical level, FD shows a high phenotype variability. Cardiovascular dysfunction is often recurrent or, in some cases, is the sole symptom (cardiac variant) representing the leading cause of death in Fabry patients. Cardiac dysfunction is dependent on globotriaosylceramide (Gb3) accumulation in the heart but several other mechanisms are involved, such as inflammation and mitochondrial dysfunction, that could become useful targets for therapeutics.
Entry Collection : Rare Monogenic Diseases
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Topic review
Updated time: 17 May 2021
Submitted by: Vicente Andres
Definition: Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease that recapitulates many symptoms of physiological aging and precipitates death. Patients develop severe vascular alterations, mainly massive vascular smooth muscle cell loss, vessel stiffening, calcification, fibrosis, and generalized atherosclerosis, as well as electrical, structural, and functional anomalies in the heart. As a result, most HGPS patients die of myocardial infarction, heart failure, or stroke typically during the first or second decade of life. No cure exists for HGPS, and therefore it is of the utmost importance to define the mechanisms that control disease progression in order to develop new treatments to improve the life quality of patients and extend their lifespan. Since the discovery of the HGPS-causing mutation, several animal models have been generated to study multiple aspects of the syndrome and to analyze the contribution of different cell types to the acquisition of the HGPS-associated cardiovascular phenotype.
Entry Collection : Rare Monogenic Diseases
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Topic review
Updated time: 25 Jun 2021
Submitted by: Antonina Giammanco
Definition: Hyperalphalipoproteinemia (HALP) is a lipid disorder characterized by elevated plasma high-density lipoprotein cholesterol (HDL-C) levels above the 90th percentile of the distribution of HDL-C values in the general population. Secondary non-genetic factors such as drugs, pregnancy, alcohol intake, and liver diseases might induce HDL increases. Primary forms of HALP are caused by mutations in the genes coding for cholesteryl ester transfer protein (CETP), hepatic lipase (HL), apolipoprotein C-III (apo C-III), scavenger receptor class B type I (SR-BI) and endothelial lipase (EL).
Entry Collection : Rare Monogenic Diseases
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Topic review
Updated time: 30 Apr 2021
Submitted by: Sara Tucci
Definition: Mitochondria are the powerhouse of the cells, generating up to 90% of the energy within a cell in the form of adenosine triphosphate (ATP). There is a close connection between fatty acid metabolism and mitochondria, involving a considerable number of cellular processes that go well beyond mitochondrial fatty acid metabolism. Fatty acids are essential for ATP and energy production, and are therefore highly relevant in the regulation of energy homeostasis. The processes of β-oxidation, linked to ATP production, and mitochondrial fatty acid biosynthesis (mtFAS) are both localized in the mitochondria. This last pathway, in particular, produces molecules that are used as cellular structural components for post-translational modifications of proteins and in signaling cascades.
Entry Collection : Rare Monogenic Diseases
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Topic review
Updated time: 19 Jul 2021
Submitted by: Masashi Mizuguchi
Definition: The mammalian target of the rapamycin (mTOR) system regulates various cellular functions, such as growth, proliferation, metabolism and survival/death. In systemic organs, it is critically involved in multiple processes, including neurogenesis, nutrition and immunity. In the brain, its roles are essential in the cerebral cortical development, synaptic functions, and brain activities such as learning, cognition and social functions.
Entry Collection : Rare Monogenic Diseases
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Topic review
Updated time: 30 Jun 2021
Submitted by: Julien Van-Gils
Definition: The Rubinstein-Taybi syndrome (RSTS) is a rare congenital developmental disorder characterized by a typical facial dysmorphism, distal limb abnormalities, intellectual disability, and many additional phenotypical features. It occurs at between 1/100,000 and 1/125,000 births.
Entry Collection : Rare Monogenic Diseases
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Topic review
Updated time: 04 Jun 2021
Submitted by: Adrian Dockery
Definition: Inherited retinal diseases (IRDs) represent a collection of phenotypically and genetically diverse conditions. IRDs phenotype(s) can be isolated to the eye or can involve multiple tissues. These conditions are associated with diverse forms of inheritance, and variants within the same gene often can be associated with multiple distinct phenotypes. Such aspects of the IRDs highlight the difficulty met when establishing a genetic diagnosis in patients. Here we provide an overview of cutting-edge next-generation sequencing techniques and strategies currently in use to maximise the effectivity of IRD gene screening. These techniques have helped researchers globally to find elusive causes of IRDs, including copy number variants, structural variants, new IRD genes and deep intronic variants, among others.
Entry Collection : Rare Monogenic Diseases
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Topic review
Updated time: 24 May 2021
Submitted by: Nabila Jabrane-Ferrat
Definition: Endosome-derived small extracellular vesicles (EVs), often referred to as exosomes, are produced by almost all, if not all, cell types, and are critical for intercellular communication. They are composed of a lipid bilayer associated with membrane proteins and contain a payload of lipids, proteins and regulatory RNAs that depends on the parental cell physiological condition. By transferring their “cargo”, exosomes can modulate the phenotype of neighboring and distant cells. Stem cells (SC) were widely studied for therapeutic applications regarding their regenerative/reparative potential as well as their immunomodulatory properties. Whether from autologous or allogeneic source, SC beneficial effects in terms of repair and regeneration are largely attributed to their paracrine signaling notably through secreted EVs. Subsequently, SC-derived EVs have been investigated for the treatment of various diseases, including inflammatory skin disorders, and are today fast-track cell-free tools for regenerative/reparative strategies.
Entry Collection : Rare Monogenic Diseases
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Topic review
Updated time: 17 Jun 2021
Submitted by: Dirk Hubmacher
Definition: Secreted a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS) proteases play crucial roles in tissue development and homeostasis. The biological and pathological functions of ADAMTS proteases are determined broadly by their respective substrates and their interactions with proteins in the pericellular and extracellular matrix. For some ADAMTS proteases, substrates have been identified and substrate cleavage has been implicated in tissue development and in disease. For other ADAMTS proteases, substrates were discovered in vitro, but the role of these proteases and the consequences of substrate cleavage in vivo remains to be established. Mutations in ADAMTS10 and ADAMTS17 cause Weill–Marchesani syndrome (WMS), a congenital syndromic disorder that affects the musculoskeletal system (short stature, pseudomuscular build, tight skin), the eyes (lens dislocation), and the heart (heart valve abnormalities). WMS can also be caused by mutations in fibrillin-1 (FBN1), which suggests that ADAMTS10 and ADAMTS17 cooperate with fibrillin-1 in a common biological pathway during tissue development and homeostasis.
Entry Collection : Rare Monogenic Diseases
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