June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
OPA1 deletions account for 26% of cases with autosomal dominant optic atrophy (ADOA, Kjer disease)
Author Affiliations & Notes
  • Xavier ZANLONGHI
    Centre Hospitalier Universitaire de Rennes, Rennes, Bretagne, France
  • Guy Lenaers
    University Angers, Angers, France
  • Majida charif
    Genetics and Immuno-Cell Therapy Team, Morocco
  • Anne Barrucand
    Centre Hospitalier Universitaire de Rennes, Rennes, Bretagne, France
  • Agnès GUICHET
    University Angers, Angers, France
  • Pascal Reynier
    University Angers, Angers, France
  • Valèrie Desquiret-Dumas
    University Angers, Angers, France
  • Patrizia Amati-Bonneau
    University Angers, Angers, France
  • Footnotes
    Commercial Relationships   Xavier ZANLONGHI None; Guy Lenaers None; Majida charif None; Anne Barrucand None; Agnès GUICHET None; Pascal Reynier None; Valèrie Desquiret-Dumas None; Patrizia Amati-Bonneau None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4112. doi:
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      Xavier ZANLONGHI, Guy Lenaers, Majida charif, Anne Barrucand, Agnès GUICHET, Pascal Reynier, Valèrie Desquiret-Dumas, Patrizia Amati-Bonneau; OPA1 deletions account for 26% of cases with autosomal dominant optic atrophy (ADOA, Kjer disease). Invest. Ophthalmol. Vis. Sci. 2023;64(8):4112.

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

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Purpose : Because a large fraction of our ADOA cases lacked a molecular diagnosis, in spite of having a typical family history in most cases, we analyzed OPA1 gene by MLPA to complement results related to NGS sequencing. We investigated 6 index patients diagnosed with ADOA clinical grounds who were negative for OPA1 mutations, and identified large OPA1 deletions. We compared the phenotype of these 6 families with a haplo-insufficiency pathophysiological mechanism, with the phenotypes related to other OPA1 mutations.

Methods : A monocentric French cohort of 119 patients (51 family) with typical clinical AOD underwent a full ophthalmic examination. Informed consent was obtained from each patient and unaffected relatives. The diagnosis was based on routine clinical procedures, the standard being refraction and determination of best corrected visual acuity, color vision testing (15 hue), OCT RNFL and fundus photography. Using classical molecular diagnosis based on Sanger sequencing of OPA1 exons, NOH panel sequencing, exome sequencing or OPA1 gene sequencing, we identified 45 index patients with an OPA1 mutation, while 6 families remained negative. Using MLPA analysis, we found a loss of heterozygosity for 5 SNPs related to a deletion of exon 30 in 5 families, and a deletion of exons 27 to 30 for the sixth family.

Results : For the 119 patients, the mean age in years was 37.74 years, being 32.39 for the large deletion cohort and 39.62 for the other mutation cohort.
The best corrected visual acuity in LogMar is 0.59 (right eye), 0.57 (left eye) for the large deletion group, 0.73 (right eye), 0.69 (left eye) for the other mutation group. No statistically significant difference for the visual acuities of the right eyes and left eyes, and for the 15-hue color test vision was observed between the 2 groups. For the RNFL OCT, ISNT analyses, there was no statistically significant difference between the 2 groups.

Conclusions : Using an MLPA technique in a monocentric French population, OPA1 genomic deletions were found in more than 25% of 119 patients (6 families out of 51) of ADOA cases, while no phenotypic difference was observed between patients with a OPA1 large deletion or another mutation. Our findings suggest that an analysis of OPA1 genomic rearrangements with MLPA technique is mandatory for the investigation and diagnosis of ADOA.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.


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