connective tissue disorder 1 Flashcards
Describe Ehlers-Danlos syndrome (EDS)
A group of heritable connective tissue disorders primarily affecting collagen-encoding genes or genes encoding collagen-modifying enzymes, characterized by symptoms like joint hypermobility, scoliosis, fragile skin, and cardiovascular abnormalities.
What are some characteristic symptoms of Ehlers-Danlos syndrome?
Joint hypermobility, scoliosis, fragile and extremely elastic skin (bruises, scarring, wound healing impairment), cardiovascular abnormalities.
Define the prognosis of Ehlers-Danlos syndrome
The prognosis varies depending on the severity of the specific subtype of the syndrome.
Do you know when the classification of Ehlers-Danlos syndrome began?
The classification of EDS started in the 1960s, with novel subtypes being increasingly discovered since 1998.
Describe the historical figures associated with Ehlers-Danlos syndrome
Edvard Ehlers and Henri-Alexandre Danlos are historically linked to the syndrome, with the syndrome named after them.
Describe the Berlin classification of Ehlers Danlos syndrome in 1988.
It included 11 different forms based on clinical findings, mode of inheritance, and biochemical alterations.
What are the main types in Villefranche classification of Ehlers Danlos syndrome in 1997?
Classical (Types I, II), Hypermobility (Type III),ascular (Type IV), Kyphoscoliosis (Type VI), Dermatosperaxis (Type VIIC), Arthrochlasia (Type VIIA, VIIB).
How many types are included in the 2017 International Classification of Ehlers Danlos Syndromes?
Thirteen types based on 19 genes.
Define the purpose of the International Classification of Ehlers Danlos Syndromes in 2017.
It guides genetic counseling for the different types.
Do the classifications of Ehlers Danlos syndrome differ in terms of the basis for categorization?
Yes, they differ based on clinical findings, mode of inheritance, biochemical alterations, and genetic basis.
Describe the evolution of the classification of Ehlers Danlos syndrome from 1988 to 2017.
It progressed from the Berlin classification with 11 forms to the Villefranche classification with 6 main types, and finally to the 2017 International Classification with 13 types based on genetic factors.
Describe Ehlers Danlos syndrome.
A genetic disorder caused by mutations affecting Collagens I, III, and V, with 40-50% of mutations found in COL5A1 or COL5A2.
What is haploinsufficiency in the context of Ehlers Danlos syndrome?
When one copy of the gene responsible for collagen production is inactivated or deleted, leading to reduced protein production.
How does a mutation in Collagen V impact collagen assembly in Ehlers Danlos syndrome?
It affects the initiation of type I collagen fibril assembly, leading to changes in fibril diameter and tissue properties.
Define ECM in the context of Ehlers Danlos syndrome.
Extracellular matrix, which is severely affected in composition, elasticity, and wound healing in EDS patients.
What role does Collagen type V play in collagen assembly in Ehlers Danlos syndrome?
It controls the initiation of type I collagen fibril assembly, acting as a template for developing type I collagen fibrils.
Do mutations in Ehlers Danlos syndrome result in changes in the material properties of affected tissues?
Yes, mutations lead to changes in the average fibril diameter and material properties of tissues.
Describe the impact of Ehlers Danlos syndrome on collagen assembly and the cell surface.
It revisits dogmas related to collagen assembly and its interaction with the cell surface, as discussed in Musiime et al’s study in Cells, 2021.
What is the impact of reduced hydroxylysine formation in Kyphoscoliosis (VI) in Ehlers Danlos syndrome?
Reduced hydroxylysine formation leads to reduced stability of the collagen triple helix.
Define PLOD-1 in the context of Ehlers Danlos syndrome.
PLOD-1 stands for procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1, which controls the production of lysyl hydroxylase 1.
How does PLOD-1 contribute to collagen production in Ehlers Danlos syndrome?
PLOD-1 is required for the hydroxylation of specific lysine residues to hydroxylysines, which are precursors for the cross-linking process essential for collagen’s tensile strength.
What is the role of ADAMTS-2 in dermatosperaxis (VIIc) form of EDS?
ADAMTS-2 is a procollagen peptidase that fails to cleave procollagen and form fibrils in dermatosperaxis (VIIc) form of EDS.
Define ADAMTS in the context of EDS.
ADAMTS stands for A Disintegrin And Metalloproteinase with ThromboSpondin domains, involved in processing pre-procollagen molecules into procollagen.
How are rare forms of EDS linked to defects in collagen processing?
Rare forms of EDS are caused by defects in collagen processing, leading to issues in the formation of collagen fibrils.
What is the consequence of the failure to cleave procollagen in EDS?
The failure to cleave procollagen in EDS results in the inability to form collagen fibrils properly.
What is the main mutation associated with vascular forms of Ehlers Danlos syndrome?
Vascular forms of EDS are primarily associated with a mutation in the COL3A1 gene, which affects the production of type III collagen.
How does type III collagen interact with type I collagen in Ehlers Danlos syndrome?
Type III collagen forms heterotypic fibrils with type I collagen and serves as a ‘template’ for the formation of type I collagen, especially during development.
Define the substitution that occurs in Ehlers Danlos syndrome affecting the collagen molecule.
In Ehlers Danlos syndrome, there is a substitution of glycine (GLY) which can affect almost the entire collagen molecule, leading to various symptoms.
Describe the impact of COL3A1 mutation in Ehlers Danlos syndrome on skin and blood vessels.
The COL3A1 mutation in Ehlers Danlos syndrome can lead to fragility of the skin and blood vessels, as well as affect skin elasticity and other related symptoms.
What is the focus of the study by Eble et al. in 2009 related to Ehlers Danlos syndrome?
The study by Eble et al. in 2009 focuses on the extracellular matrix (ECM) of blood vessels in the context of Ehlers Danlos syndrome.
Describe the techniques used for human skin histology in the provided.
Array of techniques including histological section stained with haematoxylin-eosin and higher magnification stained with Fontana–Masson picrosirius histochemical method (FMPS).
What are the different layers of the skin mentioned in the content?
Epidermis, Papillary dermis, Reticular dermis, Hypodermis.
What is the title of the article mentioned in the content related to skin tissue engineering quality controls?
Basic Quality Controls Used in Skin Tissue Engineering by Laura Linares-Gonzalez et al. in Life, 2021.
Describe the observation of collagen fibrils in the skin sample of Ehlers Danlos syndrome type IV (Vascular) using TEM.
Collagen fibrils in the skin sample are irregular, have different diameters, and the organization of space between fibrils is inconsistent.
What can cause variable clinical phenotypes including acrogeria and vascular rupture in Ehlers Danlos syndrome type IV (Vascular)?
COL3A1 mutations.
Define Ehlers Danlos syndrome type IV (Vascular) and specify the affected area mentioned in the content.
It is a type of EDS that affects the arteries.
How did Pope et al. contribute to the study of Ehlers Danlos syndrome type IV (Vascular)?
They published a study in the British Journal of Dermatology in 1996 regarding the syndrome.
Do collagen fibrils in the skin sample of EDS type IV (Vascular) exhibit consistent organization between them?
No, the organization between collagen fibrils is not consistent.
Describe the process of collagen fibril observation via TEM mentioned in the content.
Observation of collagen fibrils in skin samples and fibroblast cultures using Transmission Electron Microscopy (TEM), revealing irregular fibrils with different diameters and a cauliflower-like appearance, along with inconsistent organization and spacing between fibrils.
Define Ehlers Danlos syndrome.
A group of genetic connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility due to defects in collagen synthesis.
How is Osteogenesis imperfecta type III/Ehlers-Danlos overlap syndrome described in the content?
Described as a condition in a Chinese man exhibiting features of both Osteogenesis imperfecta type III and Ehlers-Danlos syndrome, suggesting an overlap or combination of symptoms from both disorders.
What is the significance of the study by Lu et al. in Intractable and rare diseases research, 2018?
The study likely contributes to the understanding of Ehlers Danlos syndrome and collagen-related disorders through the observation of collagen fibrils via TEM in a Chinese man with overlapping symptoms of different connective tissue disorders.
Do collagen fibrils in the mutant mice exhibit any differences compared to the control group as mentioned in the content?
Yes, the collagen fibrils in the mutant mice show irregularities such as different diameters, cauliflower-like appearance, and inconsistent organization and spacing between fibrils, unlike the control group.
Describe the findings related to collagen fibrils in the study by Wenstrup et al. published in JBC, 2004.
The study likely discusses observations of collagen fibrils in a specific context, possibly highlighting structural abnormalities or variations in collagen organization or composition.
How are collagen fibrils described in the content in terms of their appearance and organization?
Collagen fibrils are described as irregular, with different diameters, resembling cauliflower shapes, and showing inconsistent organization and spacing between fibrils.
Define Transmission Electron Microscopy (TEM) and its role in the study.
TEM is a microscopy technique that uses electrons to visualize the ultrastructure of samples at a very high resolution, allowing for detailed observation of collagen fibrils in skin samples and fibroblast cultures in this study.
What is observed in collagen fibril observation via TEM in Ehlers Danlos syndrome?
Collagen fibril observation via TEM in Ehlers Danlos syndrome involves examining collagen fibrils in skin samples or fibroblast cultures.
Define a Novel Splice Variant in the N-propeptide of COL5A1 in the context of Ehlers Danlos syndrome.
A Novel Splice Variant in the N-propeptide of COL5A1 refers to a genetic mutation that causes an EDS phenotype with severe kyphoscoliosis and eye involvement.
How is stress-strain analysis used in Ehlers Danlos syndrome research?
Stress-strain analysis is used to study the abnormal tendon ultrastructure and mechanics in classical Ehlers Danlos syndrome.
Describe the findings of Rie Harboe Nielsen et al. in FASEB J 2014 regarding Ehlers Danlos syndrome.
Rie Harboe Nielsen et al. in FASEB J 2014 reported abnormal tendon ultrastructure and mechanics in classical Ehlers Danlos syndrome.
Describe the difference in molecular weight between Alpha 1 and Alpha 2 chains in Ehlers Danlos syndrome on SDS-PAGE electrophoresis.
Alpha 1 chain has a higher molecular weight (~138 kDa) compared to Alpha 2 chain (100-140 kDa).
What does it indicate when intracellular products in SDS-PAGE electrophoresis have a lower molecular weight but appear more intense?
It suggests that these products are present in higher quantity.
Define SDS-PAGE electrophoresis and its role in studying Ehlers Danlos syndrome.
SDS-PAGE electrophoresis is a technique used to separate proteins based on their molecular weight. In Ehlers Danlos syndrome, it helps analyze the molecular characteristics of collagen chains.
How does the retention of Alpha chains at the top of the gel in SDS-PAGE electrophoresis relate to Ehlers Danlos syndrome?
In Ehlers Danlos syndrome, the Alpha chains have a higher molecular weight, causing them to be retained at the top of the gel during electrophoresis.
Do patients with Ehlers Danlos syndrome secrete more products to the media or retain more intracellularly compared to controls in SDS-PAGE electrophoresis?
Patients with Ehlers Danlos syndrome retain more products intracellularly than controls, even though they also secrete some products to the media.
Describe the difference between the control and patient panels in the sequencing data provided.
The control panel is compared to the patient panel.
What type of nucleotide change (C-T transition) occurred in the sequencing data, leading to a change from Arginine to Cysteine?
A C-T transition resulted in the codon change.
Define the consequence of the Cysteine substitution for collagen synthesis.
The Cysteine substitution leads to the projection of Cysteine outside the collagen helix, forming disulphide bridges between adjacent collagen molecules.
How is Cysteine positioned in the collagen helix due to the mutation described in the content?
Cysteine is projected outside of the helix.
What is the significance of the mutation in Type I Collagen for Classical EDS according to the content?
Classical EDS is caused by a mutation in Type I Collagen.
Describe what DSC thermograms are.
D thermograms are graphs that show the changes in heat capacity of a substance as a function of temperature.
Describe the content of Lecture 1 on locomotor system disorders.
Lecture 1 covers the fundamentals of locomotor system disorders.
What is the focus of Lecture 2 regarding inherited monogenic connective tissue diseases?
Lecture 2 focuses on inherited monogenic connective tissue diseases I.
What is the main topic discussed in Lecture 3 about inherited monogenic connective tissue diseases?
Lecture 3 delves into inherited monogenic connective tissue diseases II.
