Mutations in the TOPORS gene cause 1% of autosomal dominant retinitis pigmentosa.
OBJECTIVE
The purpose of this project was to determine if mutations, including large insertions or deletions, in the recently identified RP31 gene topoisomerase I-binding arginine-serine rich (RS) protein (TOPORS), cause an appreciable fraction of autosomal dominant retinitis pigmentosa (adRP).


METHODS
An adRP cohort of 215 families was used to determine the frequency of TOPORS mutations. We looked for mutations in TOPORS by testing 89 probands from the cohort without mutations in other known adRP genes. Mutation detection was performed by fluorescent capillary sequencing and by multiplex ligation probe amplification.


RESULTS
Two different TOPORS mutations, p.Glu808X and p.Arg857GlyfsX9, were each identified in one proband. Patients with these mutations exhibited clinical signs typical of advanced adRP. No large deletions or insertions of TOPORS were identified in our study.


CONCLUSIONS
Point mutations and small insertions or deletions in TOPORS cause approximately 1% of adRP. Large deletions or insertions of TOPORS are not an appreciable cause of adRP. Contrary to previous reports, no distinct clinical phenotype was seen in these patients.
Bowne
Sara J
SJ
The University of Texas Health Science Center, Human Genetics Center, School of Public Health, Houston, TX 77030, USA. sara.j.bowne@uth.tmc.edu
Sullivan
Lori S
LS
Gire
Anisa I
AI
Birch
David G
DG
Hughbanks-Wheaton
Dianna
D
Heckenlively
John R
JR
Daiger
Stephen P
SP
D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012174:Retinitis Pigmentosa / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C120157:TOPORS protein, human; D044767:Ubiquitin-Protein Ligases