De novo mutation in the RP1 gene (Arg677ter) associated with retinitis pigmentosa.
OBJECTIVE
The Arg677ter mutation in the RP1 gene is one of the most common causes of autosomal dominant retinitis pigmentosa (RP). In the current study, a de novo Arg677ter RP1 gene mutation was identified in a patient with RP.


METHODS
RP1 gene mutation screening was performed in probands with simplex RP. In one proband with the RP1 mutation, paternity was established by analyzing 24 short tandem repeat polymorphisms. Additional candidate RP genes, including rhodopsin, RDS/peripherin, RP2, and RPGR, were also examined in this proband. Phenotype was characterized with psychophysics, electroretinography, and optical coherence tomography.


RESULTS
An RP1 (Arg677ter) mutation was identified in one of the patients with simplex RP, but the sequence change was not detected in his parents. Parentage was confirmed, and other candidate genes were negative for mutations. Retinal function and cross-sectional imaging studies in the patient indicated greater rod than cone dysfunction with a photoreceptor basis for the abnormalities.


CONCLUSIONS
The de novo origin of an RP1 (Arg677ter) mutation in a patient with simplex RP suggests that this common autosomal dominant RP mutation can arise independently in the population and supports the hypothesis of a mutational hotspot in the RP1 gene.
Schwartz
Sharon B
SB
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Aleman
Tomas S
TS
Cideciyan
Artur V
AV
Swaroop
Anand
A
Jacobson
Samuel G
SG
Stone
Edwin M
EM
D000328:Adult; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007368:Interferometry; D008027:Light; D008297:Male; D008869:Microtubule-Associated Proteins; D010375:Pedigree; D017354:Point Mutation; D011110:Polymorphism, Genetic / Q000235:genetics; D011601:Psychophysics; D012160:Retina / Q000502:physiology; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D020080:Tandem Repeat Sequences; D014054:Tomography; D014794:Visual Fields
D005136:Eye Proteins; D008869:Microtubule-Associated Proteins; C120042:RP1 protein, human