April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Homozygosity Mapping Identifies A Novel Locus For An Unusual Form Of Leber Congenital Amaurosis
Author Affiliations & Notes
  • Ahmed A. Basheikh
    McGill Ocular Genetics Laboratory, McGill University Health Centre, Montreal, Quebec, Canada
  • Julie Racine
    McGill Ocular Genetics Laboratory, McGill University Health Centre, Montreal, Quebec, Canada
  • Irma Lopez
    McGill Ocular Genetics Laboratory, McGill University Health Centre, Montreal, Quebec, Canada
  • Huanan Ren
    McGill Ocular Genetics Laboratory, McGill University Health Centre, Montreal, Quebec, Canada
  • Mahshad Darvish
    McGill Ocular Genetics Laboratory, McGill University Health Centre, Montreal, Quebec, Canada
  • Silvin Bakalian
    McGill Ocular Genetics Laboratory, McGill University Health Centre, Montreal, Quebec, Canada
  • Anneke den Hollander
    Human Genetics, Ophthalmology,
    Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  • Frans P. Cremers
    Human Genetics,
    Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  • Robert K. Koenekoop
    McGill Ocular Genetics Laboratory, McGill University Health Centre, Montreal, Quebec, Canada
  • Footnotes
    Commercial Relationships  Ahmed A. Basheikh, None; Julie Racine, None; Irma Lopez, None; Huanan Ren, None; Mahshad Darvish, None; Silvin Bakalian, None; Anneke den Hollander, None; Frans P. Cremers, None; Robert K. Koenekoop, None
  • Footnotes
    Support  CIHR, FFB-Canada, FRSQ, NIH and Reseau Vision.
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 65. doi:
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      Ahmed A. Basheikh, Julie Racine, Irma Lopez, Huanan Ren, Mahshad Darvish, Silvin Bakalian, Anneke den Hollander, Frans P. Cremers, Robert K. Koenekoop; Homozygosity Mapping Identifies A Novel Locus For An Unusual Form Of Leber Congenital Amaurosis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):65.

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Abstract

Purpose: : To identify the molecular genetic cause underlying a severe retinal dystrophy consisting of congenital blindness with nystagmus, variable severe macular colobomas and choroidal osteoma in 3 siblings of a consanguineous Vietnamese family.

Methods: : Patients were phenotyped by projected Snellen acuities, ERGs, retinal photography, in vivo microscopy (Spectralis OCT, Heidelberg), fundus autofluorescence (FAF), and kinetic perimetry. Known autosomal recessive retinitis pigmentosa and Leber congenital amaurosis (LCA) mutations (18 genes, 585 mutations) were excluded using APEX technology. We performed homozygosity mapping using 660K SNPs. Positional candidate genes were identified using the UCSC human genome browser. Bioinformatics, gene ontology, interpro domain comparisons, and gene expression profiling were performed to identify and rank functional candidates.

Results: : The three affected members had severe visual impairment ranging between counting fingers at 1 foot and hand motion vision, nystagmus and large central or ring scotomas. Fundus exam showed normal optic discs, narrow vessels, marked beaten metal changes, maculopathy and bone spicules. One patient had a peripapillary choroidal osteoma. OCT & FAF showed variable severe photoreceptor destruction, concentrated in the macular region. One patient had a deep macular coloboma. The rod-mediated ERG was not detectable, while a 5 uV cone-mediated ERG could still be recorded. The largest homozygous regions of the 3 sibs overlap on chromosome 3, in a 2.1 Mb region containing 15 genes thus far not implicated in LCA or RP. We identified 12 other retinal dystrophy patients with large homozygous regions overlapping this locus.

Conclusions: : We describe a novel retinal dystrophy phenotype in a Vietnamese family, and identified a homozygous region on chromosome 3, which does not overlap with known retinal dystrophy loci or genes. Finding this retinal dystrophy gene will improve our understanding of photoreceptor development, health and death.

Keywords: gene screening • photoreceptors • retinal degenerations: hereditary 
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