April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
A cone-rod dystrophy patient with a homozygous RP1L1 mutation
Author Affiliations & Notes
  • Shuhei Kameya
    Ophthalmology, Chiba Hokusoh Hosp Nippon Med Sch, Inba, Japan
  • Sachiko Kikuchi
    Ophthalmology, Chiba Hokusoh Hosp Nippon Med Sch, Inba, Japan
  • Kiyoko Gocho
    Ophthalmology, Chiba Hokusoh Hosp Nippon Med Sch, Inba, Japan
  • Said El Shamieh
    Genetics, INSERM, U968, CNRS, UMR_7210, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris F-75012,, France
  • Keiichiro Akeo
    Ophthalmology, Chiba Hokusoh Hosp Nippon Med Sch, Inba, Japan
  • Yuko Sugawara
    Ophthalmology, Honjo Daiichi Hospital, Yurihonjo, Japan
  • Kunihiko Yamaki
    Ophthalmology, Chiba Hokusoh Hosp Nippon Med Sch, Inba, Japan
  • Christina Zeitz
    Genetics, INSERM, U968, CNRS, UMR_7210, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris F-75012,, France
  • Isabelle Audo
    Genetics, INSERM, U968, CNRS, UMR_7210, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris F-75012,, France
  • Hiroshi Takahashi
    Ophthalmology, Nippon Medical School, Sendagi, Japan
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3276. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Shuhei Kameya, Sachiko Kikuchi, Kiyoko Gocho, Said El Shamieh, Keiichiro Akeo, Yuko Sugawara, Kunihiko Yamaki, Christina Zeitz, Isabelle Audo, Hiroshi Takahashi; A cone-rod dystrophy patient with a homozygous RP1L1 mutation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3276.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: To describe a family with a cone-rod dystrophy (CRD) carrying a homozygous mutation in the RP1-like protein 1 (RP1L1) gene.

Methods: A family including one subject affected with CRD and three unaffected members without evidence of consanguinity underwent detailed ophthalmic and clinical evaluations including high-resolution imaging of retinal morphology by adaptive optics (AO) fundus camera. Mutation screening of the coding sequence of RP1L1 was performed by DNA sequencing analysis. Five computational assessment tools were used to predict the protein function (SIFT, Polyphen2, Align GVGD, PMut). In order to investigate other putative pathogenic variant(s), a next-generation-sequencing (NGS) approach was applied to the CRD patient with an exon sequencing array targeting 121 known genes underlying retinal diseases.

Results: The patient showed a mild reduction of cone and flicker response in full-field electroretinogram (ERG). Her ERG also showed slight decrease in the amplitude of rod responses. Elipsoid and interdigitation zone on spectral-domain optical coherence tomography (SD-OCT) images were severely disturbed. Focal macular ERGs showed a reduced amplitude of the a- and b-wave. Multifocal ERGs (mfERGs) responses were severely reduced. AO images of the patient showed severe reduction of cone density and irregular cone mosaic. A homozygous RP1L1 mutation (c.3628 T>C) was identified in the patient. The mutation c.3628 T>C in exon 4 resulted in the substitution of proline for serine at amino acid position 1210 (p.S1210P). The serine at position 1210 is well conserved among the RP1L1 family in other mammalian species. Four out of five computational assessment tools predicted that this mutation is damaging to the protein function. This mutation was not present in 460 Japanese control alleles. Family members with heterozygous p.S1210P mutation showed normal best-corrected visual acuity, SD-OCT, mfERGs, focal macular ERGs, and AO analysis. The NGS approach only identified missense changes at the heterozygous state in PCDH15 (p.P923L), RPGRIP1 (p.V1211I), and GPR98 (p.L2422F), which did not co-segregate with the phenotype or /and were predicted to be benign.

Conclusions: We have demonstrated a possibility that autosomal recessive cone-rod dystrophy may be caused by homozygous RP1L1 mutations.

Keywords: 539 genetics • 688 retina • 507 electrophysiology: 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.

×