May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Non-Syndromic Autosomal Recessive Cone-Rod Dystrophy in a Consanguineous Family Carrying a Novel Splice Site Mutation in the MERTK Gene
Author Affiliations & Notes
  • H. P. Scholl
    Dept. of Ophthalmology, University of Bonn, Bonn, Germany
  • P. Charbel Issa
    Dept. of Ophthalmology, University of Bonn, Bonn, Germany
  • I. Ebermann
    Institute of Human Genetics,
    University Hospital of Cologne, Cologne, Germany
  • M. Walger
    Department of Otorhinolaryngology, Head and Neck Surgery,
    University Hospital of Cologne, Cologne, Germany
  • G. Nurnberg
    Cologne Center for Genomics,
    University of Cologne, Cologne, Germany
    RZPD Deutsches Ressourcenzentrum für Genomforschung GmbH, Berlin, Germany
  • R. Lang-Roth
    Department of Otorhinolaryngology, Head and Neck Surgery,
    University Hospital of Cologne, Cologne, Germany
  • C. Becker
    Cologne Center for Genomics,
    University of Cologne, Cologne, Germany
    RZPD Deutsches Ressourcenzentrum für Genomforschung GmbH, Berlin, Germany
  • P. Nurnberg
    Cologne Center for Genomics,
    Institute for Genetics,
    University of Cologne, Cologne, Germany
  • F. G. Holz
    Dept. of Ophthalmology, University of Bonn, Bonn, Germany
  • H. J. Bolz
    Institute of Human Genetics,
    University Hospital of Cologne, Cologne, Germany
  • Footnotes
    Commercial Relationships H.P. Scholl, None; P. Charbel Issa, None; I. Ebermann, None; M. Walger, None; G. Nurnberg, None; R. Lang-Roth, None; C. Becker, None; P. Nurnberg, None; F.G. Holz, None; H.J. Bolz, None.
  • Footnotes
    Support DFG BO 2954/1-1; DFG Heisenberg fellowship SCHO 734/2-1; EU FP6, Integrated Project "EVI-GENORET" (LSHG-CT-2005-512036); Koeln Fortune Program, grant 113/2004; National Genome Research Network (NGFN).
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3207. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      H. P. Scholl, P. Charbel Issa, I. Ebermann, M. Walger, G. Nurnberg, R. Lang-Roth, C. Becker, P. Nurnberg, F. G. Holz, H. J. Bolz; Non-Syndromic Autosomal Recessive Cone-Rod Dystrophy in a Consanguineous Family Carrying a Novel Splice Site Mutation in the MERTK Gene. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3207. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose:: To describe the phenotype of a consanguineous family segregating autosomal recessive cone-rod dystrophy (CORD).

Methods:: All family members underwent detailed clinical investigation including best-corrected visual acuity, slit lamp examination, stereoscopic funduscopy and digital fundus photography, Goldmann kinetic visual fields, electroretinography, fundus autofluorescence imaging (cSLO, HRA-2, Heidelberg engineering, Heidelberg, Germany), and high-resolution OCT (SOCT, Optopol, Torun, Poland).

Results:: CORD in this family was mapped to chromosome 2q13-q14.1. We have identified homozygosity for a novel splice site mutation in the MERTK gene, c.2189+1G>T, resulting in skipping of exon 16 and a consecutive frameshift. Detailed ophthalmological investigation of the six siblings revealed severe CORD in five of them. They all exhibited a very similar phenotype, which was least severe in the youngest sibling (II:1) and most advanced in the oldest (II:6). FAF imaging revealed spotted increased FAF at the posterior pole in II:1 and, to a lesser degree, in II:3. The older siblings showed patches of decreased FAF. SOCT revealed reduced central retinal thickness, disrupted photoreceptor layer and a granular appearance of the RPE layer. Audiological investigation indicated hair cell and vestibular dysfunction in two siblings affected by CORD and in one witout retinal degeneration. Subsequent linkage and mutation analysis revealed a mutation in a non-syndromic hearing loss gene.

Conclusions:: Although MERTK is generally considered an RP gene, these data confirm recent reports that extended the phenotypic spectrum to severe CORD (McHenry et al. IOVS 2004;45:1456-1463; Tschernutter et al. BJO 2006;90:718-723). The phenotypic severity of the CORD in the siblings correlated well with age. The FAF and SOCT findings may indicate that in early stages of the disease reduced RPE phagocytosis results in multifocal autofluorescent photoreceptor debris accumulating between the outer retina and the RPE. In later stages, photoreceptor and RPE cell death would occur as observed in the central macula of the affected individuals.

Keywords: retinal degenerations: hereditary • genetics • imaging/image analysis: clinical 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×