June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
An intronic deletion in the PROM1 gene leads to autosomal recessive cone-rod dystrophy
Author Affiliations & Notes
  • Tamar Ben-Yosef
    Genetics Dept - Faculty of Med, Technion, Haifa, Israel
  • Osnat Eidinger
    Genetics Dept - Faculty of Med, Technion, Haifa, Israel
  • Rina Leibu
    Ophthalmology, Rambam Medical Center, Haifa, Israel
  • Hadas Newman
    Ophthalmology, Tel-Aviv Medical Center, Tel Aviv, Israel
  • Leah Rizel
    Genetics Dept - Faculty of Med, Technion, Haifa, Israel
  • Ido Perlman
    Ophthalmology, Tel-Aviv Medical Center, Tel Aviv, Israel
    Physiology & Biophysics, Faculty of Medicine-Technion, Haifa, Israel
  • Footnotes
    Commercial Relationships Tamar Ben-Yosef, None; Osnat Eidinger, None; Rina Leibu, None; Hadas Newman, None; Leah Rizel, None; Ido Perlman, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2898. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Tamar Ben-Yosef, Osnat Eidinger, Rina Leibu, Hadas Newman, Leah Rizel, Ido Perlman; An intronic deletion in the PROM1 gene leads to autosomal recessive cone-rod dystrophy . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2898.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: To investigate the genetic basis for autosomal recessive cone-rod dystrophy (CRD) in a consanguineous Israeli Jewish family.

Methods: Patients underwent a detailed ophthalmic examination, including funduscopy, electroretinography (ERG), visual field testing and optical coherence tomography (OCT). Genome-wide homozygosity mapping using a SNP array was performed to identify homozygous regions shared among two of the affected individuals. Mutation screening of the underlying gene was carried out by direct sequencing. In silico and in vitro analyses were used to predict the effect of the identified mutation on splicing.

Results: The affected family members are three siblings suffering from progressive visual deterioration, glare, deficient color vision and night vision abnormalities. Visual field tests revealed central scotomas of different extension. Both cone and rod ERG responses were reduced, with cones being more severely affected. Homozygosity mapping revealed several homozygous intervals shared among two of the affected individuals. One of them included the PROM1 gene. Sequence analysis of the 26 coding exons of PROM1 in one affected individual revealed no mutations in the coding sequence or in intronic splice-sites. However, in intron 21, proximate to the intron-exon junction, we observed a homozygous10 bp deletion between positions -26 and -17 (c.2281-26_-17del). This deletion co-segregated with the disease in the family, and was not detected in public databases nor in 101 ethnically-matched control individuals. In silico analysis predicted that this deletion would lead to altered intron 21 splicing. Bioinformatic analysis predicted that a recognition site for the SRSF2 splicing factor is located within the deleted sequence.<br />

Conclusions: Here we report a novel and unique intronic mutation of PROM1, underlying autosomal recessive CRD in a consanguineous Israeli family. Altered splicing probably results from deletion of a recognition site for the SRSF2 splicing factor. This report expands the spectrum of pathogenic mutations of PROM1 and further demonstrates the importance of intronic mutations.

×
×

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.

×