June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
How genetic instability in choroideremia-specific iPSc uncovered a segregating translocation.
Author Affiliations & Notes
  • Nejla Erkilic
    Inserm U1051, Montpellier, Herault, France
  • Pauline Bouret
    CHRU, Montpellier, France
  • Simona Torriano
    Inserm U1051, Montpellier, Herault, France
  • Krishna Damodar
    Inserm U1051, Montpellier, Herault, France
  • Christian P Hamel
    Inserm U1051, Montpellier, Herault, France
  • Franck Pellestor
    CHRU, Montpellier, France
  • Vasiliki Kalatzis
    Inserm U1051, Montpellier, Herault, France
  • Footnotes
    Commercial Relationships   Nejla Erkilic, None; Pauline Bouret, None; Simona Torriano, None; Krishna Damodar, None; Christian Hamel, None; Franck Pellestor, None; Vasiliki Kalatzis, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2296. doi:
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      Nejla Erkilic, Pauline Bouret, Simona Torriano, Krishna Damodar, Christian P Hamel, Franck Pellestor, Vasiliki Kalatzis; How genetic instability in choroideremia-specific iPSc uncovered a segregating translocation.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2296.

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

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Purpose : Induced pluripotent stem cells (iPSc) have revolutionised the field of retinal research. In particular, iPSc-derived retinal pigment epithelium (RPE) has been shown to be morphologically and functionally characteristic of the RPE in vivo. Furthermore, we have shown that iPSc-derived RPE from a choroideremia patient mimics the biochemical phenotype and represents a powerful model to test the efficacy of novel therapies. Choroideremia is an X-linked disorder due to mutations in the CHM gene. We recently generated iPSc from two affected brothers carrying a deletion of the CHM gene. As the iPSc reprogramming and culture is known to generate chromosomal rearrangements, karyotype analysis was systematically performed prior to retinal differentiation.

Methods : We performed a punch skin biopsy of two brothers with choroideremia. We used Sendai viral vectors carrying the Yamanaka transcription factor cocktail to reprogram the fibroblasts into iPSc. Karyotype analyses were performed on selected clones from passage 10.

Results : In three clones, we detected complex structural rearrangements, and/ or aneuploidy involving chromosomes 12 and 20, as well as, in two of the three clones, chromosome 5. Common to these three clones was the balanced translocation t(12;20)(q24.3;q11.2). Furthermore, in three additional clones, we detected only this translocation. To determine if it arose during iPSc generation, we performed a karyotype analysis of the original fibroblasts and detected the same translocation. To exclude a culture artefact, we performed karyotype analyses on blood samples from all the family members (father, mother, three brothers and one sister). All four children carry the deletion of the CHM gene inherited from their mother. In addition, we detected the translocation t(12;20)(q24.3;q11.2) in the father, in the two probands, and in their sister. Only the remaining son did not carry the translocation.

Conclusions : A genetic instability already present in somatic cells leads to further instability following reprogramming into iPSc. This allowed us to uncover a previously undetected balanced translocation segregating in a choroideremia family. This has important implications for genetic counselling as balanced translocations are a cause of recurrent miscarriages. This study represents a novel outcome following the generation of patient-specific iPSc.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.


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