Dominant retinitis pigmentosa associated with two rhodopsin gene mutations. Leu-40-Arg and an insertion disrupting the 5'-splice junction of exon 5.
OBJECTIVE
To determine the phenotypes of two families in which retinitis pigmentosa cosegregates with a rhodopsin (RHO) gene mutation: a leucine-to-arginine change at codon 40 (Leu-40-Arg) in one family, and a 150-base pair insertion that disrupts the RHO 5'-splice junction of exon 5 in another.


METHODS
Three affected members of each family.


RESULTS
The Leu-40-Arg mutation was associated with the onset of night blindness in the first decade of life. By the fourth decade, severe retinal functional loss was evident on dark-adapted static threshold perimetry, and electroretinographic responses were absent or barely detectable. In contrast, the RHO 150-base pair insertion was associated with the later onset of mild night vision difficulties; in two individuals, mild night vision difficulties were first noticed in the second decade while a third, a 25-year-old woman, was asymptomatic. Dark-adapted static threshold perimetry of this latter individual revealed a "regional" or class 2 pattern of retinal functional loss associated with equal loss of rod and cone electroretinographic responses.


CONCLUSIONS
The RHO Leu-40-Arg mutation causes symptomatic retinal dysfunction by the end of the first decade while the insertion disrupting the 5'-splice junction of RHO exon 5 causes later onset "regional" or class 2 retinal dysfunction.
Kim
R Y
RY
Department of Clinical Ophthalmology, Institute of Ophthalmology, London, England.
al-Maghtheh
M
M
Fitzke
F W
FW
Arden
G B
GB
Jay
M
M
Bhattacharya
S S
SS
Bird
A C
AC
D000328:Adult; D001120:Arginine; D003623:Dark Adaptation; D004596:Electroretinography; D005091:Exons; D005260:Female; D005654:Fundus Oculi; D006801:Humans; D007930:Leucine; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D012326:RNA Splicing / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology; D012243:Rhodopsin / Q000235:genetics*; D014792:Visual Acuity; D014794:Visual Fields
D012243:Rhodopsin; D001120:Arginine; D007930:Leucine