July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
A novel mutation in KIF3B in a family with dominant retinitis pigmentosa and polydactyly
Author Affiliations & Notes
  • Stephen P Daiger
    Human Genetics Center, School Pub Hlth, Univ Texas Hlth Sci Ctr Houston, Houston, Texas, United States
    Ruiz Dept. of Ophthalmology and Visual Science, The Univ. of Texas Health Science Center, Houston, Texas, United States
  • Lori S Sullivan
    Human Genetics Center, School Pub Hlth, Univ Texas Hlth Sci Ctr Houston, Houston, Texas, United States
  • Sara J Bowne
    Human Genetics Center, School Pub Hlth, Univ Texas Hlth Sci Ctr Houston, Houston, Texas, United States
  • Elizabeth L Cadena
    Human Genetics Center, School Pub Hlth, Univ Texas Hlth Sci Ctr Houston, Houston, Texas, United States
  • Kinga Maria Bujakowska
    Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
  • Eric A Pierce
    Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
  • Michael B Gorin
    Jules Stein Eye Institute and Dept. of Ophthalmology, Univ. of California Los Angeles, Los Angeles, California, United States
  • Xénia Latypova
    Center for Human Disease Modeling, Duke Univ. Medical Center, Durham, North Carolina, United States
  • Erica E Davis
    Center for Human Disease Modeling, Duke Univ. Medical Center, Durham, North Carolina, United States
  • Nicholas Katsanis
    Center for Human Disease Modeling, Duke Univ. Medical Center, Durham, North Carolina, United States
  • Ludovic Martin
    Center for Human Disease Modeling, Duke Univ. Medical Center, Durham, North Carolina, United States
  • Laurence Legeai-Mallet
    Université Paris Descartes, Sorbonne Paris Cité, Paris, France
    Hôpital Necker-Enfants Malades, Paris, France
  • Benjamin Cogne
    CHU de Nantes, Nantes, France
  • Stéphane Bezieau
    CHU de Nantes, Nantes, France
  • Thomas Besnard
    CHU de Nantes, Nantes, France
  • Bertrand Isidor
    CHU de Nantes, Nantes, France
  • Footnotes
    Commercial Relationships   Stephen Daiger, None; Lori Sullivan, None; Sara Bowne, None; Elizabeth Cadena, None; Kinga Bujakowska, None; Eric Pierce, None; Michael Gorin, None; Xénia Latypova, None; Erica Davis, None; Nicholas Katsanis, None; Ludovic Martin, None; Laurence Legeai-Mallet, None; Benjamin Cogne, None; Stéphane Bezieau, None; Thomas Besnard, None; Bertrand Isidor, None
  • Footnotes
    Support  NIH Grant EY007142 and grants from the Foundation Fighting Blindness, the Wiliam Stamps Farish Fund and the Hermann Eye Fund.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 47. doi:
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      Stephen P Daiger, Lori S Sullivan, Sara J Bowne, Elizabeth L Cadena, Kinga Maria Bujakowska, Eric A Pierce, Michael B Gorin, Xénia Latypova, Erica E Davis, Nicholas Katsanis, Ludovic Martin, Laurence Legeai-Mallet, Benjamin Cogne, Stéphane Bezieau, Thomas Besnard, Bertrand Isidor; A novel mutation in KIF3B in a family with dominant retinitis pigmentosa and polydactyly. Invest. Ophthalmol. Vis. Sci. 2018;59(9):47.

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

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Abstract

Purpose : Whole-exome next-generation sequencing (NGS) was used to identify the cause of disease in a large family with a dominant form of retinitis pigmentosa.

Methods : Whole-exome NGS was performed on two affected female cousins. Sanger sequencing was used to confirm variants of interest. Linkage LOD scores were calculated based on results from eight affected family members.

Results : A large, six-generation family segregating both retinitis pigmentosa and polydactyly was tested as part of our large adRP cohort. Sanger sequencing of known adRP genes and NGS of a retinal gene panel had been performed previously by several laboratories on different family members and failed to identify a disease mutation. Exome sequencing of two cousins revealed a novel, potentially pathogenic variant in the KIF3B gene (NP_004789.1; p.Leu523Pro). All affected family members tested carried the variant; to date it has not been observed in any control population. The p.Leu523Pro mutation is predicted to be pathogenic and is located in the stalk between the motor domain and the tail of the kinesin protein. Linkage analysis in the extended family using the novel variant as a marker results in a LOD score of 4.2 at 0% recombination.

Conclusions : A novel mutation in the KIF3B gene is the likely cause of retinitis pigmentosa in a six-generation Ashkenazi Jewish family. All patients with the KIF3B mutation in the family exhibit classic symptoms of retinitis pigmentosa with an average age of onset in the first decade. Several affected members of the family have polydactyly; others are reported to have various forms of kidney dysfunction. Observation of these additional findings is suggestive of a ciliopathy and is consistent with a mutation in a kinesin gene. The KIF3B protein, along with KIF3A, is part of the heterotrimeric kinesin-2 complex and is required for anterograde transport along the connecting cilia of photoreceptors. Numerous genes critical for ciliary function and intraflagellar transport (IFT) have been identified as causes of retinal degeneration, both with and without additional ciliopathy findings.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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