A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration.

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • MA Maw - , University of Otago (Author)
  • D Corbeil - , Heidelberg University , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • A Hellwig - , Heidelberg University , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • JC Wilson-Wheeler - , University of Otago (Author)
  • RJ Bridges - , University of Otago (Author)
  • G Kumaramanickavel - , Sankara Nethralaya Eye Hospital (Author)
  • D Nancarrow - , The Park Centre for Mental Health (Author)
  • K Röper - , Heidelberg University , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • A Weigmann - , Heidelberg University , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • WB Huttner - , Heidelberg University , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • MJ Denton - , University of Otago (Author)

Abstract

The disks of vertebrate photoreceptors are produced by outgrowths of the plasma membrane. Hence genes that encode retinal proteins targeted to plasma membrane protrusions represent candidates for inherited retinal degenerations. One such candidate is the gene encoding human prominin (mouse)-like 1 (PROML1, previously known as AC133 antigen) which belongs to the prominin family of 5-transmembrane domain proteins. Murine prominin (prom) shows a strong preference for plasma membrane protrusions in a variety of epithelial cells whereas PROML1 is expressed in retinoblastoma cell lines and adult retina. In the present study, molecular genetic analyses of a pedigree segregating for autosomal recessive retinal degeneration indicated that the affected individuals were homozygous for a nucleotide 1878 deletion in PROML1. This alteration is predicted to result in a frameshift at codon 614 with premature termination of translation. Expression of a similar prom deletion mutant in CHO cells indicated that the truncated protein does not reach the cell surface. Immunocytochemistry revealed that prom is concentrated in the plasma membrane evaginations at the base of the outer segments of rod photoreceptors. These findings suggest that loss of prominin causes retinal degeneration, possibly because of impaired generation of the evaginations and/or impaired conversion of the evaginations to disks.

Details

Original languageEnglish
Pages (from-to)27-34
Number of pages8
JournalHuman molecular genetics
Volume9
Issue number1
Publication statusPublished - Jan 2000
Peer-reviewedYes
Externally publishedYes

External IDs

PubMed 10587575
Scopus 0034101383

Keywords