Human Genetics

, Volume 113, Issue 3, pp 268–275 | Cite as

Novel types of mutation in the choroideremia (CHM) gene: a full-length L1 insertion and an intronic mutation activating a cryptic exon

  • José A. J. M. van den Hurk
  • Dorien J. R. van de Pol
  • Bernd Wissinger
  • Marc A. van Driel
  • Lies H. Hoefsloot
  • Ilse J. de Wijs
  • L. Ingeborgh van den Born
  • John R. Heckenlively
  • Han G. Brunner
  • Eberhart Zrenner
  • Hans-Hilger Ropers
  • Frans P. M. Cremers
Original Investigation


Choroideremia (CHM) is a progressive chorioretinal degeneration caused by mutations in the widely expressed CHM gene on chromosome Xq21. The product of this gene, Rab escort protein (REP)-1, is involved in the posttranslational lipid modification and subsequent membrane targeting of Rab proteins, small GTPases that play a key role in intracellular trafficking. 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. In 35 patients, at least 21 different causative CHM defects were identified. These included two partial CHM gene deletions and an insertion of a full-length L1 retrotransposon into the coding region of the CHM gene, a type of mutation that has not been previously reported as a cause of CHM. We also detected nine different nonsense mutations, five of which are recurrent, a small deletion, a small insertion, and at least five distinct splice site mutations, one of which has been described previously. Moreover, we report for the first time the identification of an intronic mutation remote from the exon-intron junctions that creates a strong acceptor splice site and leads to the inclusion of a cryptic exon into the CHM mRNA. Finally, in an affected male who did not have a mutation in any of the CHM exons or their splice sites, the deletion of a complete exon from the CHM mRNA was observed.


Splice Site Intronic Mutation Single Strand Conformation Polymorphism Analysis Cryptic Exon Choroideremia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We would like to thank E.A. Sistermans, A.J.L.G. Pinckers, A.S. Plomp, E.M. Bleeker-Wagemakers, K. Rüther, M. Seeliger, U. Kellner, G. Matthijs, K. Baerlocher, and M. Jay for providing us with patient samples or clinical data. We also wish to thank S. van der Velde-Visser and B. van den Helm for tissue culturing and I.C. Meij for technical assistance and for a critical reading of the manuscript. This work was supported by the Netherlands Organization for Scientific Research (NWO).


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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • José A. J. M. van den Hurk
    • 1
  • Dorien J. R. van de Pol
    • 1
  • Bernd Wissinger
    • 2
  • Marc A. van Driel
    • 3
  • Lies H. Hoefsloot
    • 1
  • Ilse J. de Wijs
    • 1
  • L. Ingeborgh van den Born
    • 4
  • John R. Heckenlively
    • 5
  • Han G. Brunner
    • 1
  • Eberhart Zrenner
    • 2
  • Hans-Hilger Ropers
    • 6
  • Frans P. M. Cremers
    • 1
  1. 1.Department of Human GeneticsUniversity Medical Center NijmegenNijmegenThe Netherlands
  2. 2.University Eye HospitalTübingenGermany
  3. 3.Center for Molecular and Biomolecular InformaticsUniversity of NijmegenNijmegenThe Netherlands
  4. 4.The Rotterdam Eye HospitalRotterdamThe Netherlands
  5. 5.Jules Stein Eye InstituteUCLA School of MedicineLos AngelesUSA
  6. 6.Max Planck Institute for Molecular GeneticsBerlinGermany

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