Genetic Collagen Disorders

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Genetic Collagen Disorders Osteogenesis
Imperfecta Ehlers Danlos Syndrome There are
others.
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Types of collagen

• Type I (most common) In bone, scar tissue,
  tendons, ligaments.
• Type II Hyaline cartilage.
• Type III Found in the extracellular matrix of
  earl granulation (wound healing) tissue replaced
  by type I coll. In mature scar tissue.
• Type IV Lens of eye basal lamina beneath
  epithelium (esp. in skin, beneath epidermis)
  capillaries, including glomeruli.
• Type V Interstitial tissue (loose conective
  tissue) placenta.
• List goes up to XXVIII28

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Collagen Structure Right handed helix of 3
subunits. Each subunit is a LH helix (not an
a-helix which is RH). Handednes of a helix
fingers show sense of rotation when travelling in
direction that thumb points.
Julian Voss-Andreae "Unraveling Collagen a
metaphor for aging and growth
http//en.wikipedia.org/wiki/ImageCollagentripleh
elix.png
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Osteogenesis Imperfecta

• General definition Genetic bone disorder in
  which bones are weak and fragile.
• Various subtypes have been defined more
  specifically.
• Symptoms
• Type I (most common, mildest) Bone fragility,
  blue sclerae. Multiple fractures with minimal
  cause.
• Type II Severe deformity and bone weakness
  death near time of birth due to respiratory
  insufficiency.
• Type III Progressive skeletal deformity of limbs
  through childhood, and of spine in late
  childhood/early adolescence. Sclerae often
  normal.

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Osteogenesis Imperfecta, type III

Craig W. Wiesenhutter www.cdaarthritis.com/images_
slides
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Osteogenesis Imperfecta

• Cause
• Mutation to collagen gene, usually to alpha
  subunit of type I collagen gene. Usually
  autosomal dominant, inherited occasionally de
  novo.
• Type I Collagen is relatively normal (by some
  biochemcial tests) but present in reduced
  amounts. Due to mutations that affect
  post-transcriptional- and/or post-translational
  processing more than the folding of the final
  product.
• Type II Low amount and low quality of
  collagen.
• Type III Collagen is present in normal amounts,
  but of insufficient quality. Often due to
  mutation in gene for alpha subunit of type I
  collagen which prevents normal triple helix from
  forming.

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Osteogenesis Imperfecta
OI type II , type III mutation in collagen gene
? normal collagen triple helix doesnt form
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Ehlers Danlos Syndrome
General definition Joint hypermobility with skin
changes Various subtypes have been defined more
specifically. Symptoms Unstable, flexible joints
(hypermobility) with a tendency to dislocate and
subluxate, due to ligaments which are overly
stretchable. Elastic, fragile, soft skin that
easily forms welts and scars. Intense pain where
the joints dislocate is very common. Cause Mutati
on to collagen gene, usually to type I or type V
collagen gene. Autosomal dominant.
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Ehlers Danlos Syndrome
20-year-old man presented for consideration of
repair of a rectal prolapse that had been present
since birth. Physical examination revealed
hyperelasticity of the skin (Panel A) with easy
bruisability, hypermobility of the joints (Panel
B), and a rectal prolapse of about 15 cm in
length, which was easily reducible. Results of
laboratory tests and chromosome studies were
normal. Results of a skin biopsy showed
disorganization of collagen bundles in the
dermis. Chen and Jao (2007), NEJM 357 (11) e12.
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Marieb Hoehn 4.7. Proteoglycan or aggrecan.
Key component of the ground substance of
cartilage. Made of proteins and GAGs chondroitin
sulfate, keratan sulfate.
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Protein core
Craig W. Wiesenhutter www.cdaarthritis.com/images_
slides