Collagen Structure and Function Part 2 Flashcards
“Brittle Bone Disease” – an inherited disorder involving mutations in collagens or molecules regulating collagen biosynthesis. The patients have extremely weak undermineralized bones that fracture easily.
Osteogenesis Imperfecta (OI)
an inherited type of dentin dysplasia in which the teeth are discolored and translucent. The teeth are weaker and susceptible to rapid wear. Some OI patients exhibit this disease
Dentinogenesis Imperfecta
an inherited connective tissue disorder in which there is increased skin laxity, joint hypermobility, vascular abnormalities.
Ehlers-Danlos Syndrome
a mutation that results in reduced amounts of a protein rather than the complete absence of the protein or the production of a mutant protein
Hypomorphic mutation
a mouse strain which has been genetically modified by the artificial introduction of genetic material into every cell.
Transgenic Mouse
the genetic trait is carried on one of the autosomal chromosomes (i.e. not the X or Y chromosome). An individual need only carry one copy of the mutated gene in order to manifest the disease phenotype
Autosomal Dominant Inheritance
the genetic trait is carried on one of the autosomal chromosomes (i.e. not the X or Y chromosome). An individual needs to carry two copies of the mutated gene in order to manifest the disease phenotype (i.e. both alleles of the gene must be mutated).
Autosomal Recessive Inheritance
a condition in which the patient usually dies in early infancy (immediately after birth up to about 4 weeks after birth).
Perinatal Lethal
the presence of two or more populations of cells that have different genotypes in a single individual who has developed from one fertilized egg. One population of the cells carries the mutation. If the mutation is passed on to offspring, this implies that the mosaicism is “germline” – meaning that some or all of the sperm or oocytes carry the mutation. can result from a mutation or aberrant chromosomal translocation, separation or duplication in one cell of the embryo during development. The mutation is then passed on only to the daughter cells that derived from that mutated cell, which will represent a certain fraction of the adult cells. Genetic mosaics are distinguished from “Chimeras” in which two or more genotypes arise in one individual due to the fusion of more than one fertilized zygote.
Mosaic for mutation (mosaicism)
inflammation of the kidney
Glomerulonephritis
a fancy word for a small oral opening (mouth)
Microstomia
When type 1 collagen goes wrong, what occurs?
Osteogenesis imperfecta
Hereditary disease where bones are extremely brittle and break often for little or no apparent cause; caused by autosomal dominant mutations in COLIA1 and COLIA2
Osteogenesis imperfecta
T/F: Classical Osteogenesis Imperfecta is due to QUANTITATIVE or QUALITATIVEAbnormalities of Type I Collagen
True
OI type where bones are predisposed to fracture; blue sclera; autosomal dominant; results in functional null of one of the COLIA genes that results in reduced amounts of normal collagen 1`
OI type 1
OI type that is the most severe; numerous fractures; short stature; autosomal dominant; results in abnormal pro-alpha collagen chains which become incorporated into collagen trimers therefore no normal collagen trimers are produced
Type 2 OI
OI type where there is severe bone deformity and is usually autosomal dominant; progressive deforming type
Type 3 OI
OI type severe intermediate between types 1 and 3; autosomal dominant; mutations in COLIA2 mostly
Type IV OI
Why are many diseases with mutations in ECM proteins inherited in a dominant fashion?
ECM form polymeric structure; normal when abnormal ones are incorporated
OI type that is autosomal dominant but had no mutations in collagen genes
Type V OI
Prolyl-3-hydroxylation is in the collagen ________ chain
alpha 1 chain
____ null mutations result in a severe lethal form of OI
CRTAP
OI Type caused by hypomorphic CRTAP defect
Type VII OI
Mutations in CRTAP cause defective ________ which delays collagen folding
3-prolyl-hydroxylation
______ deficiency causes a recessive metabolic bone disorder resembling lethal/severe OI
Prolyl 3-hydroxylase 1
Lack of _____ is seen in OI with normal collagen folding
cyclophilin B
OI can be caused by mutations in _____ collagen genes or in genes encoding proteins involved in collagen post-translational modifications/ regulation of collagen biosynthesis
type I collagen
Hereditary disease of dentin with opalescent brown teeth that wear easily, bulbous crowns, narrow roots, small/obliterated pulp chambers, and frequent splitting of enamel from dentin under occlusal stress
dentinogenesis imperfecta
Shields Type 2 and 3 DI are due to mutations in _____
DSPP
T/F: OI patients are more susceptible to wear/breakage and or enamel fracturing from teeth
True
long term use of ______ in OI patients can be associated with osteonecrosis of Jaw in cancer patients on high dose bp
bisphosphonates
___ is associated with abnormal collagen biosynthesis due to nutritional deficiency in Vit C
scurvy
lethargy, bleeding gums/mucus membranes, fragile blood vessels/petechial hemorrhage of skin, loss of gingival and periodontal collagen fibers/ anchoring fibers (loosening of teeth), and bone pain are symptoms of _____
scurvy
____ important co factor for prolyl and lysyl hydroxylases that hydoxylate proline/lysine residues
Vit C
T/F: If hydroxylation doesn’t occur due to lack of Vit C, procollagen doesn’t fold correctly which leads to deficient collagen assembly and the inability to renew CT matrix
True
______ are related to mutations in collagen and genes in collagen biosynthetic pathway
Ehlers Danlos Syndromes
_____ are characterized by fragility of CTs, manifestations of skin, ligaments, joints, blood vessels, internal organs; clinical spectrum varies from mild skin and joint hyperlaxity to severe physical disability/life threatening complications; mild skeletal abnormalities
Ehlers Danlos syndrome
___ has 7 subtypes mostly linked to mutations in genes encoding fibrillar collagens
Ehlers Danlos syndrome
____ is mutation in N-proteinase cleavage site in COLIA2 gene
Ehlers Danlos skin
What happens when type 2 collagen goes wrong?
Chondrodysplasias
____ is characterized by death prenatally or in first weeks of life, short barrel shaped trunk, very short extremeties, large head soft cranium, flat face, underossification of axial skeleton, hypercellular epiphysela cartilage, poorly organized or absent growth plate, diminished ECM, and thick irregular collagen fibrils
Achondrogenesis type 2/ hypochondrogenesis
___ involve replacement of glycine by a bulkier amino acid in triple helical region alpha 1 (II) chain
Achondrogenesis type 2/ hypochondrogenesis
___ syndrome is characterized by glomerulonephritis and is seen with issues in collagen 4
alport syndrome
____ is a congenital form of muscular dystrophy
Bethlem myopathy
A type VII collagen knockout is seen in _____
Epidermolysis Bullosa
____ is an autoimmune disease; autoantibodies are produced against non collagenous domains of type 4 collagen alpha 3 chain; leads to problems with kidney filtration, blood in urine, burning sensation when urinating, nephriting, coughing up blood, fatigue, and nausea
Goodpasture syndrome
