Disease relevance of Choroideremia

• Two genetic diseases involve the Rab geranylgeranylation machinery: choroideremia, an X-linked retinal degeneration resulting from loss-of-function mutations in REP1, and gunmetal, a mouse model of Hermansky-Pudlak syndrome resulting from mutations in the alpha-subunit of RGGT [1].
• Mutations in the REP-1 gene in humans lead to an X-chromosome-linked defect known as choroideremia, a progressive disease that inevitably culminates in complete blindness [2].
• Patients with Usher syndrome, choroideremia or cone-rod dystrophy are most often given the diagnosis of retinitis pigmentosa [3].
• Less common retinal findings included retinal detachment, abnormal retinal pigmentation, progressive atrophy of the RPE simulating choroideremia and lattice degeneration [4].
• In the past 10 y, there have been considerable advances in the mapping, isolation, and characterization of many genes for important ocular conditions: retinitis pigmentosa, Norrie disease, Waardenburg syndrome, choroideremia, aniridia, retinoblastoma, and others [5].

High impact information on Choroideremia

• Mutations in members of this family, such as REP-1, lead to abnormalities, including progressive retinal degradation (choroideremia) in humans [6].
• Using semisynthetic fluorescent Rab27A, we demonstrate that although Rab27A can be prenylated by REP-2, this reaction can be effectively inhibited by other Rab proteins, providing a possible explanation for the accumulation of unprenylated Rab27A in choroideremia [6].
• Human choroideremia protein contains a FAD-binding domain [7].
• In contrast to what has been observed before for the loss of function of the choroideremia gene, the depletion of Mrs6p from yeast cells blocks vesicular transport [8].
• Two patients with deletions and choroideremia are affected by an X-linked mixed conductive/sensorineural deafness; one patient, XL-62, was confirmed at surgery to have DFN3, while the other patient, XL-45, is suspected clinically to have the same disorder [9].

Chemical compound and disease context of Choroideremia

• Macular pigment and lutein supplementation in choroideremia [10].
• Fluorescein angiography in potential carriers for choroideremia. An additional aid for final diagnosis, when funduscopy shows equivocal symptoms [11].

Biological context of Choroideremia

• Consequently, conditional rescue of the embryonic lethal phenotype of the rep-1 mutation may provide a faithful mouse model for choroideremia [12].
• Deficient geranylgeranylation of Ram/Rab27 in choroideremia [13].
• Fourteen families with choroideremia (TCD) have been examined for linkage to nine genetic markers located on the proximal long arm of the X chromosome [14].
• We have searched for mutations of the CHM gene in patients with choroideremia by analysis of individual CHM exons and adjacent intronic sequences PCR-amplified from genomic DNA and by reverse transcription (RT)-PCR analysis of the coding region of the CHM mRNA [15].
• This article describes the experimental protocol used to instruct fifteen patients with peripheral visual field loss due to retinitis pigmentosa, choroideremia, or Usher's syndrome Type II how to effectively use bioptic amorphic lenses [16].

Anatomical context of Choroideremia

• Semen was also collected from two patients with other retinal degenerations (choroideremia and fundus flavimaculatus) and patients with simplex RP [17].

Gene context of Choroideremia

• We suggest that REP-2 substitutes for the absent function of REP-1 in nonretinal cells of patients with choroideremia, thus preventing cellular dysfunction throughout the body [18].
• Choroideremia (CHM) is an X-linked progressive eye disorder which results from defects in the human Rab escort protein-1 (REP-1) gene [12].
• Choroideremia (CHM) is an X-linked retinal degenerative disease that results from mutations in Rab Escort Protein-1 (REP1) [19].
• The X-chromosomal breakpoint was located within a region where both the choroideremia locus and a deafness locus (DFN3/POU3F4) have been mapped [20].
• Recombination frequencies of 0%-4% were found between choroideremia and five markers (PGK, DXS3, DXYS12, DXS72, and DXYS1) located in Xq13-22 [21].

Analytical, diagnostic and therapeutic context of Choroideremia

• By Southern blot analysis we have mapped ten different polymorphic DNA loci relative to the position of the deletion and the choroideremia locus TCD [22].
• In general, about 60% of all the respondents had a positive attitude to the prenatal diagnosis of RP or choroideremia, though only about 30% would use if for abortion [23].
• Vitreous fluorophotometry in carriers of choroideremia and X-linked retinitis pigmentosa [24].
• METHODS: In a retrospective study, results of automated static perimetry in the central 10-degree visual field were reviewed for patients with retinitis pigmentosa and choroideremia [25].

References