May 2004
Volume 45, Issue 13
ARVO Annual Meeting Abstract  |   May 2004
L1 retrotransposition during embryogenesis in the mother of a patient with choroideremia
Author Affiliations & Notes
  • I.C. Meij
    Human Genetics/Pharmacology, UMCN Univ Medical Center, Nijmegen, The Netherlands
  • Footnotes
    Commercial Relationships  I.C. Meij, None.
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 4689. doi:
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      I.C. Meij; L1 retrotransposition during embryogenesis in the mother of a patient with choroideremia . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4689.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract: : Purpose: Choroideremia (CHM) is a progressive chorioretinal degeneration caused by mutations in the widely expressed CHM gene which is located on chromosome Xq21. The product of this gene, Rab escort protein–1, is involved in posttranslational lipid modification and subsequent membrane targeting of Rab proteins, small GTPases that play a key role in intracellular trafficking. In the course of a comprehensive mutation screen of the CHM gene, an insertion of a full–length L1 retrotransposon into CHM exon 6 was identified in a patient with choroideremia. In this study we investigated the origin and inheritance of the L1–insertion in family members of the choroideremia patient and determined the functional effect of the mutation. Methods: To determine the effect of the L1–insertion on the CHM mRNA, an RT–PCR was performed using primers in exons 5 and 8. To determine the inheritance of the L1 element, a PCR assay was developed which discriminates the mutant from the wild–type CHM alleles. Moreover, two polymorphic markers flanking exon 6 were investigated in the proband, his parents and his two sisters. His mother and sisters were analysed ophthalmologically. The L1 element was fully sequenced. Results: The L1–insertion causes an in–frame deletion of exon 6 from the CHM mRNA resulting in a protein product lacking amino acids 235 through 273. The L1–insertion was found in lymphocyte DNA of the mother of the patient but at a significantly reduced level compared to the normal product. The L1 element was not found in a phenotypically normal sister of the proband although marker analysis revealed that she had inherited the same CHM gene haplotype as her brother. Conclusions: These results show that the mother of the choroideremia patient is a germline and somatic mosaic for the L1–insertion and that the mutation occurred in an early stage of embryogenesis. These findings provide the first evidence consistent with an L1 retrotransposition event during embryogenesis.

Keywords: chorioretinitis • genetics • mutations 

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