Choroideremia

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Choroideremia

• Ian MacDonald
• University of Alberta

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Choroideremia

• A form of retinitis pigmentosa
• X-linked recessive inheritance
• Female carriers exhibit signs
• Degeneration of all the layers of the retina
• Progressive loss of peripheral vision over 35
  years while preserving central vision

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Young man with choroideremia
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CHM carrier femalepatchy areas of chorioretinal
atrophy
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Family studies
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The hunt for the gene

• Three groups studied families to find the gene
• Lewis and Nussbaum (USA)
• Cremers (Netherlands)
• MacDonald (Canada)

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The CHM gene

• The gene was found by Cremers and Lewis groups
  in 1990 through DNA analysis
• Seabra (Texas) simultaneously identified the gene
  by protein analysis as Rab escort protein-1
• Geranylgeranyl transferase
• Role in addition of lipid molecules to proteins
  (Rabs)
• Function in delivery of nutrients across cells

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With 2F-1 monoclonal (anti-REP1)

• Apical labeling of RPE Bruchs membrane

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Protein analysis

• All mutations or changes in the gene result in
  the absence of REP-1
• Antibody against REP-1 can detect the absence of
  REP-1 in white blood cells from males with
  choroideremia

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Gene transfer - lymphocytes from CHM male
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Acknowledgments
Collaborators Dick Lewis Miguel Seabra Paul
Sieving Sam Jacobson Richard Weleber John
Heckenlively Alex Levin Elias Traboulsi Jacquie
Greenberg

• Funding
• CIHR
• FFB Canada, US
• MSI Foundation
• National Eye Institute
• AHFMR

Laboratory Kerry McTaggart Nancy
Nesslinger Christina Sereda Sarah Flynn Ryan
Yau Thomas lee Dean Mah
Families Benelli Family Throusell Family
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Do not lose sight..
of the patients you are trying to help