May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Olfactory Dysfunction in LCA Patients With CEP290/NPHP6 Defects: A Comparison With Other RP and LCA Genotypes
Author Affiliations & Notes
  • R. K. Koenekoop
    Ophthalmology, McGill University Health Center, McGill Ocular Genetics Center, Montreal, Quebec, Canada
  • R. Hannant
    Ophthalmology & Visual Sciences and Human Genetics, Univ of Michigan-Kellogg Eye Ctr, Ann Arbor, Michigan
  • H. Khanna
    Ophthalmology & Visual Sciences and Human Genetics, Univ of Michigan-Kellogg Eye Ctr, Ann Arbor, Michigan
  • D. P. McEwen
    Ophthalmology & Visual Sciences and Human Genetics, Univ of Michigan-Kellogg Eye Ctr, Ann Arbor, Michigan
  • P. Jenkins
    Ophthalmology & Visual Sciences and Human Genetics, Univ of Michigan-Kellogg Eye Ctr, Ann Arbor, Michigan
  • C. Brown
    Ophthalmology, McGill University Health Center, McGill Ocular Genetics Center, Montreal, Quebec, Canada
  • A. I. den Hollander
    Human Genetics, Raboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  • F. P. M. Cremers
    Human Genetics, Raboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  • J. Martens
    Dept of Pharmacology, University of Michigan, Ann Arbor, Michigan
  • A. Swaroop
    Ophthalmology & Visual Sciences and Human Genetics, Univ of Michigan-Kellogg Eye Ctr, Ann Arbor, Michigan
  • Footnotes
    Commercial Relationships R.K. Koenekoop, None; R. Hannant, None; H. Khanna, None; D.P. McEwen, None; P. Jenkins, None; C. Brown, None; A.I. den Hollander, None; F.P.M. Cremers, None; J. Martens, None; A. Swaroop, None.
  • Footnotes
    Support FFB-C and FRSQ (RKK and FPMC); NIH – EY07961, FFB and RPB (AS)
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3725. doi:
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      R. K. Koenekoop, R. Hannant, H. Khanna, D. P. McEwen, P. Jenkins, C. Brown, A. I. den Hollander, F. P. M. Cremers, J. Martens, A. Swaroop; Olfactory Dysfunction in LCA Patients With CEP290/NPHP6 Defects: A Comparison With Other RP and LCA Genotypes. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3725.

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

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Abstract

Purpose:: Mutations in CEP290 are a major cause of Leber congenital amaurosis (LCA). The gene is expressed in the photoreceptor cilia, and the rd16 (Cep290 in-frame deletion) mouse was recently found to be anosmic, prompting us to hypothesize that humans affected with LCA and heterozygous carriers with CEP290 mutations have olfactory dysfunction. For comparison, we wanted to investigate whether LCA and RP patients with mutations in other genes expressed in photoreceptor cilia ("the RP ciliopathies") (RPGRIP1, RPGR and USH2A) exhibit olfactory dysfunction.

Methods:: Four LCA patients and two carriers with a CEP290 p.Cys998X mutation, two LCA patients with RPGRIP1 nonsense mutations, two XLRP patients with RPGR frameshift mutations and two ARRP patients with USH2A frameshift mutations were evaluated by the University of Pennsylvania Smell Identification Test from Sensonics Inc. We used the 40 and 12 item smell tests and compared the results to 1819 normal men and 2109 normal women of various ages, after calculating the test score.

Results:: When asked, all test subjects (N=12) denied olfactory dysfunction. However, smell test results show that all four patients with CEP290 mutations had significantly abnormal olfactory dysfunction, ranging from 4/12 to 7/12 (1st percentile) and 33/40 (11th percentile) correct answers. Two heterozygous CEP290 carriers had smell test scores ranging from mild (32/40, 10th percentile) to severe microsmia (25/40, 17th percentile). RP patients with RPGR or USH2A mutations had normal olfactory function (10/12 correct answers for all). One LCA patient with RPGRIP1 mutations had normal olfactory function (10/12 correct), while a second RPGRIP1 patient was mildly abnormal (8/12 correct).

Conclusions:: LCA patients and carriers with CEP290 mutations have significant olfactory dysfunction. Not all RP/LCA patients with ciliopathies have olfactory dysfunction, however. One LCA patient with RPGRIP1 mutations had a mild olfactory dysfunction, while RP patients with RPGR, and USH2A mutations were normal. Smell testing of affected LCA patients and carriers with CEP290, RPGRIP1, RPGR and USH2A mutations may provide a simple clinical test to identify a subgroup of retinal dystrophy patients with ciliopathies.

Keywords: gene/expression • photoreceptors • retinal degenerations: hereditary 
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