RhodopsinF45L Allele Does Not Cause Autosomal Dominant Retinitis Pigmentosa in a Large Caucasian Family.
OBJECTIVE
To ascertain the potential pathogenicity of a retinitis pigmentosa (RP)-causingRHOF45L allele in a family affected by congenital achromatopsia (ACHM).


METHODS
Case series/observational study that included two patients with ACHM and 24 extended family members. Molecular genetic analysis was performed to identifyRHOF45L carrier status in the family and a control population. An adaptive optics scanning light ophthalmoscope (AOSLO) was used to image the photoreceptor mosaic and assess rod and cone structure. Spectral domain optical coherence tomography (SD-OCT) was used to examine retinal lamination. Comprehensive clinical testing included acuity, color vision, and dilated fundus examination. Electroretinography was used to assess rod and cone function.


RESULTS
Five carriers of theRHOF45L allele alone (24-80 years) and three carriers in combination with a heterozygousCNGA3mutant allele (10-64 years) were all free of the classic symptoms and signs of RP. In heterozygous carriers of both mutations, SD-OCT showed normal retinal thickness and intact outer retinal layers; rod and cone densities were within normal limits on AOSLO. The phenotype in two individuals affected with ACHM and harboring theRHOF45L allele was indistinguishable from that previously reported for ACHM.


CONCLUSIONS
TheRHOF45L allele is not pathogenic in this large family; hence, the two ACHM patients would unlikely develop RP in the future.


CONCLUSIONS
The combined approach of comprehensive molecular analysis of individual genomes and noninvasive cellular resolution retinal imaging enhances the current repertoire of clinical diagnostic tools, giving a substantial impetus to personalized medicine.
Department of Ophthalmology, New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand ; Eye Department, Greenlane Clinical Centre, Auckland District Health Board, Auckland, New Zealand.
Andrea L
AL
Vincent
Joseph
J
Carroll
Gerald A
GA
Fishman
Alexandra
A
Sauer
Dianne
D
Sharp
Phyllis
P
Summerfelt
Vesper
V
Williams
Adam M
AM
Dubis
Susanne
S
Kohl
Fulton
F
Wong
adaptive optics; exome sequencing; retinal degeneration; retinitis pigmentosa; rhodopsin mutations