Collagen Structure and Function Part 2

Question 1

“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.

Answer 1

Osteogenesis Imperfecta (OI)

Question 2

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

Answer 2

Dentinogenesis Imperfecta

Question 3

an inherited connective tissue disorder in which there is increased skin laxity, joint hypermobility, vascular abnormalities.

Answer 3

Ehlers-Danlos Syndrome

Question 4

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

Answer 4

Hypomorphic mutation

Question 5

a mouse strain which has been genetically modified by the artificial introduction of genetic material into every cell.

Answer 5

Transgenic Mouse

Question 6

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

Answer 6

Autosomal Dominant Inheritance

Question 7

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).

Answer 7

Autosomal Recessive Inheritance

Question 8

a condition in which the patient usually dies in early infancy (immediately after birth up to about 4 weeks after birth).

Answer 8

Perinatal Lethal

Question 9

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.

Answer 9

Mosaic for mutation (mosaicism)

Question 10

inflammation of the kidney

Answer 10

Glomerulonephritis

Question 11

a fancy word for a small oral opening (mouth)

Answer 11

Microstomia

Question 12

When type 1 collagen goes wrong, what occurs?

Answer 12

Osteogenesis imperfecta

Question 13

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

Answer 13

Osteogenesis imperfecta

Question 14

T/F: Classical Osteogenesis Imperfecta is due to QUANTITATIVE or QUALITATIVEAbnormalities of Type I Collagen

Answer 14

True

Question 15

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`

Answer 15

OI type 1

Question 16

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

Answer 16

Type 2 OI

Question 17

OI type where there is severe bone deformity and is usually autosomal dominant; progressive deforming type

Answer 17

Type 3 OI

Question 18

OI type severe intermediate between types 1 and 3; autosomal dominant; mutations in COLIA2 mostly

Answer 18

Type IV OI

Question 19

Why are many diseases with mutations in ECM proteins inherited in a dominant fashion?

Answer 19

ECM form polymeric structure; normal when abnormal ones are incorporated

Question 20

OI type that is autosomal dominant but had no mutations in collagen genes

Answer 20

Type V OI

Question 21

Prolyl-3-hydroxylation is in the collagen ________ chain

Answer 21

alpha 1 chain

Question 22

____ null mutations result in a severe lethal form of OI

Answer 22

CRTAP

Question 23

OI Type caused by hypomorphic CRTAP defect

Answer 23

Type VII OI

Question 24

Mutations in CRTAP cause defective ________ which delays collagen folding

Answer 24

3-prolyl-hydroxylation

Question 25

______ deficiency causes a recessive metabolic bone disorder resembling lethal/severe OI

Answer 25

Prolyl 3-hydroxylase 1

Question 26

Lack of _____ is seen in OI with normal collagen folding

Answer 26

cyclophilin B

Question 27

OI can be caused by mutations in _____ collagen genes or in genes encoding proteins involved in collagen post-translational modifications/ regulation of collagen biosynthesis

Answer 27

type I collagen

Question 28

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

Answer 28

dentinogenesis imperfecta

Question 29

Shields Type 2 and 3 DI are due to mutations in _____

Answer 29

DSPP

Question 30

T/F: OI patients are more susceptible to wear/breakage and or enamel fracturing from teeth

Answer 30

True

Question 31

long term use of ______ in OI patients can be associated with osteonecrosis of Jaw in cancer patients on high dose bp

Answer 31

bisphosphonates

Question 32

___ is associated with abnormal collagen biosynthesis due to nutritional deficiency in Vit C

Answer 32

scurvy

Question 33

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 _____

Answer 33

scurvy

Question 34

____ important co factor for prolyl and lysyl hydroxylases that hydoxylate proline/lysine residues

Answer 34

Vit C

Question 35

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

Answer 35

True

Question 36

______ are related to mutations in collagen and genes in collagen biosynthetic pathway

Answer 36

Ehlers Danlos Syndromes

Question 37

_____ 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

Answer 37

Ehlers Danlos syndrome

Question 38

___ has 7 subtypes mostly linked to mutations in genes encoding fibrillar collagens

Answer 38

Ehlers Danlos syndrome

Question 39

____ is mutation in N-proteinase cleavage site in COLIA2 gene

Answer 39

Ehlers Danlos skin

Question 40

What happens when type 2 collagen goes wrong?

Answer 40

Chondrodysplasias

Question 41

____ 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

Answer 41

Achondrogenesis type 2/ hypochondrogenesis

Question 42

___ involve replacement of glycine by a bulkier amino acid in triple helical region alpha 1 (II) chain

Answer 42

Achondrogenesis type 2/ hypochondrogenesis

Question 43

___ syndrome is characterized by glomerulonephritis and is seen with issues in collagen 4

Answer 43

alport syndrome

Question 44

____ is a congenital form of muscular dystrophy

Answer 44

Bethlem myopathy

Question 45

A type VII collagen knockout is seen in _____

Answer 45

Epidermolysis Bullosa

Question 46

____ 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

Answer 46

Goodpasture syndrome