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M. Garcia–Hoyos, D. Cantalapiedra, J. Gallego, D. Diego–Alvarez, E. Vallespin, R. Riveiro, M. Trujillo–Tiebas, M. Rodriguez de Alba, I. Lorda–Sanchez, C. Ayuso; New Type of Mutations in the Rep–1 Gene . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4608.
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Choroideremia (CHM; MIM 30100) is an X–linked recessive ophthalmic disease characterized by a progressive degeneration of the choroid and the pigmented epithelium of the retina. The gene associated with CHM is located on the Xq 21.2 region. The 15 exons identified in this gene span a genomic sequence of about 150kb and encode an ubiquitously expressed protein of 653aa called Rab Escort Protein (REP–1), which is indispensable for the activity of Rab geranylgeranyl–tranferase (Rab GGTase) in retinal tissue. REP proteins display high sequence similarity to GDP–dissociation inhibitor proteins (Rab GDI) and both proteins play a role in the Rab protein traffic. Different mutations, including large genomic rearrangements involving the REP–1 gene, are responsible for CHM but all of these cause truncated or absent protein.
We present the genetic and molecular characterization of 3 Spanish families clinically diagnosed of CHM. First, we have performed haplotype analyses in each family, in order to determine if the disease is linked to REP–1 gene, followed by mutational screening of the REP–1 gene at the mRNA level.
In these families, we have identified 3 novel mutations in the REP–1 gene that do not produce truncated or absent protein. The affected patients of these families have loss different parts of REP–1 protein conserved domain (domain I) that it is implicated in the interaction with Rab proteins. Our studies reveled that, in these families, the disease is due to the protein REP–1 cannot function at all, although we could confirm in 1 family, that there was protein present in the peripheral blood of the affected patients.
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