Collagen Diseases

Question 1

What is Ehlers-Danlos syndrome?

Answer 1

• Group of genetic CT disorders.
• Symptoms include: joint hypermobility, stretchy skin and skin that breaks/bruises easily.
• Caused by defect in structure, production or processing of collagen or proteins that interact with collagen.

Question 2

What is the molecular basis for Ehlers-Danlos syndrome?

Answer 2

Several different causes, e.g. Collagen type V mutation, lysyl oxidase deficiency.

Question 3

What is the molecular basis of scurvy?

Answer 3

• Vitamin C (ascorbic acid) = essential co-factor for prolyl/lysyl hydroxylase.
• Lack of VitC in diet - proline and lysine residues aren’t hydroxylated - weakened collagen as propeptides aren’t cross-linked.
• Causes poor bone formation, fragile capillaries, etc.

Question 4

What is osteogenesis imperfecta caused by?

Answer 4

• Mutation in COL1A1 or COL1A2 genes (autosomal dominant inheritance or de novo mutation).
• Absence or insufficiency of type I collagen.

Question 5

What are the symptoms of osteogenesis imperfecta?

Answer 5

1. Bones that break easily
2. Blue tinge to whites of eyes
3. Short height
4. Loose joints
5. Hearing loss
6. Breathing problems
7. Dental problems

Question 6

Why does the genetic mutation in osteogenesis imperfecta cause brittle bones?

Answer 6

• Mutation causes aa substitution of glycine to bulkier aa in the collagen triple helix…
• steric hindrance of aa side-chains…
• bulge in collagen complex…
• altered interaction between collagen fibrils and hydroxyapatite crystals.

Question 7

Why does osteogenesis imperfecta cause loss of bone mass and irregular ossification?

Answer 7

Abnormal/weaker collagen causes ineffective deposition of calcium phosphate.