11/7: Collagen Structure and Function II

Question 1

What occurs when type I collagen goes wrong?

Answer 1

Osteogenesis imperfecta

Question 2

What is osteogenesis imperfecta?

Answer 2

Brittle bone disease

Question 3

What mutation is in Osteogensis imperfecta (brittle bone disease)?

Answer 3

COL1A1 and COL1A2

Question 4

What disease is mostly autosomal dominant?

Answer 4

Type I osteogenesis imperfecta

Question 5

Classical osteogenesis imperfecta is due to ________ or _______ abnormalities of type I collagen?

Answer 5

Quantitative; qualitative

Question 6

Which type of osteogenesis imperfecta is the most common?

Answer 6

Type I osteogenesis imperfecta

Question 7

What are symptoms of type I osteogenesis imperfecta?

Answer 7

Bones predisposed to fracture (must occur before puberty)
Normal sature/ blue sclera

Question 8

What does functional null allele of COL1A1 or COL1A2 genes lead to?

Answer 8

No protein being produced from one allele

Question 9

What occurs when trimers formed?

Answer 9

Normal (encoded by normal allele), but only half the normal amount of collagen produced - QUANTITATIVE DEFICIENCY

Question 10

What kind of osteogenesis imperfecta is the most severe?

Answer 10

Type II

Question 11

What does type II osteogenesis imperfecta lead to?

Answer 11

Numerous fractures and severe bone deformity
Short stature

Question 12

What type of osteogenesis imperfecta is autosomal dominant and autosomal recessive?

Answer 12

Type II osteogenesis imperfecta

Question 13

What do mutations in COL1A1 or COL1A2 produce?

Answer 13

Abnormal pro-alpha collagen chains, which become incorporated into collagen trimers

Question 14

What type of osteogenesis imperfecta is progressive deforming type/bones fracture easily?

Answer 14

Type III

Question 15

What does type III osteogenesis imperfecta result in?

Answer 15

Short stature, spinal curvature
severe boen deformity
blue sclera
mutations in COL1A1 and COL1A2

Question 16

What type of osteogenesis imprfecta is autosomal dominant and sometimes autosomal recessive?

Answer 16

Type III osteogenesis imperfecta

Question 17

What type of osteogenesis imperfecta is an intermediate between types I and II?

Answer 17

Type IV osteogenesis imperfevta

Question 18

What type of osteogenesis imprfecta is a mutation in COL1A2 and rarely COL1A1?

Answer 18

Type IV

Question 19

What does CRTAP (Cartilage associated protein) form a complex with?

Answer 19

Cyclophilin B (PPIB)
Prolyl 3-hydroxylase 1 (LEPRE1)
and hydroxylates type I collagen

Question 20

What hydroxylates collagen alpha chain at one specific residue?

Answer 20

Prolyl-3-hydoxylase (LEPRE1)

Question 21

What does mutations in CRTAP cause?

Answer 21

defective 3-prolyl-hydroxylation (LEPRE1) which delays collagen folding

Question 22

What is type VII OI caused by?

Answer 22

hypomorphic CRTAP defect

Question 23

What does CRTAP null mutations result in?

Answer 23

Severe lethal form OI

Question 24

OI can be caused by mutations in _________ or in __________ of collagen biosynthesis

Answer 24

type 1 collagen; modifications/regulation

Question 25

What do more severe forms of OI have?

Answer 25

– Triangular shaped face – Bossing of the forehead – Low set ears – Mid face deficiency/ malocclusions – May have blue sclera

Question 26

What are oral manifestations of OI?

Answer 26

- Brown/grey tooth color (esp. primary teeth) - Abnormal pulp chamber

Question 27

What is dentinogenesis imperfecta?

Answer 27

Hereditary disease of dentin

Question 28

What are symptoms of DI?

Answer 28

-Opalescent/brown teeth that wear easily -bulbous crowns -narrow roots -Small/obliterated pulp chambers or enlarged pulp chambers -frequent splitting of enamel from dentin under occlusal stress

Question 29

What type of DI occurs in families with OI (due to mutations in COL1A1 or COL1A2)?

Answer 29

Type I DI

Question 30

What type of DI is not associated with OI (Due to mutations in DSPP)?

Answer 30

Shields Type II

Question 31

What type of DI is "brandywine" type - occurs inr acial segregation in Maryland (due to mutations in DSPP)?

Answer 31

Shields Type III

Question 32

What is a caused by opalescent/brown teeth?

Answer 32

OI

Question 33

What occurs to teeth in OI patients?

Answer 33

more susceptible to wear/breakage and/or enamel fracturing from teeth

Question 34

What is associated with abnormal collagen biosynthesis due to nutritional deficiency in Vitamin C (ascorbic acid)?

Answer 34

Scurvy

Question 35

What are symptoms of scurvy?

Answer 35

*Bleeding gums/mucous membranes *Fragile blood vessels/petechial hemorrage of skin *Loss of gingival and periodontal collagen fibers/anchoring fibers - loosening of teeth *Bone pain

Question 36

What is vitamin C an important co-factor for?

Answer 36

prolyl and lysyl hydroxylases that hydroxylate proline/lysine residues

Question 37

What occurs to unfolded procollagen if hydroxylation is prevented?

Answer 37

Retained in ER and/or degraded

Question 38

What does scurvy lead to?

Answer 38

Deficient collagen assembly- inability to renew connective tissue matrix

Question 39

What occurs when type II collagen goes wrong?

Answer 39

Chondrodysplasias

Question 40

What do mutations involving replacement of glycine by a bulkier amino acid in triple helical region of α1(II) chain cause?

Answer 40

ACGII-HCG

Question 41

What is ehlers danlos syndrome related to?

Answer 41

mutations in collagens and genes in the collagen biosynthetic pathway

Question 42

What is a result of fragility of soft CT?

Answer 42

Ehlers danlos syndrome

Question 43

What mutations is ehlers danlos linked to?

Answer 43

Mutations in genes encoding fibrillar collages (types III, V)

Question 44

What is an anti-glomerular basement antibody disease?

Answer 44

Goodpasture syndrome

Question 45

What occurs in goodpasture syndrome?

Answer 45

Autoantibodies produced against non collagenous domains of type IV collagen alpha 3 chain

Question 46

What is important in glomerular basement membrane?

Answer 46

Type IV (alpha 3)

Question 47

What does goodpasture syndrome lead to?

Answer 47

problems with kidney filtration, blood in urine, burning sensation when urinating, nephritis, coughing up blood, fatigue, nausea, etc. - can lead to acute renal failure