July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
A frameshift mutation in RDH12 causes autosomal dominant retinitis pigmentosa in families of Tunisian Jewish origin
Author Affiliations & Notes
  • Boris Rosin
    Ophthalmology, Hadassah Medical Center, Jerusalem, Israel
    The Center for Retinal and Macular Degenerations (CRMD), Hadassah Medical Center, Jerusalem, Israel
  • Prasanthi Namburi
    Ophthalmology, Hadassah Medical Center, Jerusalem, Israel
  • Muhammad Imran Khan
    Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands
  • Frans P Cremers
    Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands
  • Eyal Banin
    Ophthalmology, Hadassah Medical Center, Jerusalem, Israel
    The Center for Retinal and Macular Degenerations (CRMD), Hadassah Medical Center, Jerusalem, Israel
  • Dror Sharon
    Ophthalmology, Hadassah Medical Center, Jerusalem, Israel
  • Footnotes
    Commercial Relationships   Boris Rosin, None; Prasanthi Namburi, None; Muhammad Khan, None; Frans Cremers, None; Eyal Banin, None; Dror Sharon, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1004. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Boris Rosin, Prasanthi Namburi, Muhammad Imran Khan, Frans P Cremers, Eyal Banin, Dror Sharon; A frameshift mutation in RDH12 causes autosomal dominant retinitis pigmentosa in families of Tunisian Jewish origin. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1004.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : To characterize the genetic cause of disease and the clinical phenotype in patients with retinitis pigmentosa (RP) who belong to four apparently non-related families of Tunisian-Jewish origin with a dominant pattern of disease inheritance.

Methods : We performed genetic analysis using molecular inversion probes (MIPs) analysis and Sanger sequencing. Ocular and retinal function and structure were assessed by a full clinical ophthalmological exam, full field electroretinography, elecotrooculography and color vision testing as well as optical coherence tomography (Heidelberg Engineering GmbH), and wide-field pseudocolor and autofluorescent imaging (OPTOS system).

Results : The pedigrees demonstrated an autosomal dominant inheritance pattern, with approximately half of the family members in each generation being affected. However, examination of the candidate genes for common autosomal dominant mutations causing RP did not yield a result. In order to obtain a genetic diagnosis, we performed MIPs analysis of 109 genes known to cause inherited retinal disease and identified a heterozygous frameshift mutation (c.759del, p.Phe254Leu*24) towards the end of the open reading frame of the RDH12 gene (NM_152443.2), coding for retinol dehydrogenase 12. All affected family members exhibited clinical and electrophysiological findings typical of RP. Notably, the onset of symptoms was considerably delayed and the severity reduced in comparison to autosomal recessive cases associated with variants in the RDH12 gene. This milder phenotype was also evident in the ffERG responses, with some of the patients retaining sizable dark-adapted white flash and cone-flicker responses well into the 5th decade of life.

Conclusions : All but one reported RDH12 mutations were previously demonstrated to cause autosomal recessive Leber's congenital amaurosis and early-onset RP. Here we describe the second RDH12 mutation causing an autosomal dominant inheritance pattern in families with relatively mild RP. The mutation we identified affects the same RDH12 region as the previously described dominant frameshift mutation. We hypothesize that due to the proximity to the stop codon, the mRNA encoded by these two frameshift alleles is not recognized by the nonsense-mediated mRNA-decay and therefore not degraded, resulting in the production of an abnormal RDH12 protein that is toxic to the photoreceptor cell.

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

×
×

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.

×