Background: Pathogenic variants in the rhodopsin gene (RHO) most commonly cause
various forms of retinitis pigmentosa (RP), which is a progressive retinal degeneration,
and less commonly congenital stationary blindness (CSNB). Until now, it has been
assumed that a single variant produces either one or the other clinical outcome (e.g.
p.G90D CSNB), with rare exceptions (e.g. pE113K). Some studies have shown that
taking vitamin A can slow the progression of RP, but vitamin A treatment is not
accepted in clinical practice.
Aim: To determine whether the p.G90D causes other clinical pictures in addition to
CSNB and identify potential modifying factors associated with this.
Methods: A prospective study included all known patients harboring p.G90D in RHO
and all their family members who reported night blindness, a total of 19 patients from
three families (13 male and 6 female; median age 41 years, range 8 – 71). They
underwent an extended ophthalmologic examination which included examinations of
visual function (including electroretinography) and imaging (fundus autofluorescence
and optical coherence tomography). Patients completed a questionnare on associated
diseases and lifestyle. Serum vitamin A concentration was determined from a venous
blood sample. The pathogenic variant p.G90D was confirmed using next-generation
sequencing or Sanger sequencing.
Results: Patients had either night blindness without degeneration (NBWD) (26%),
classic RP (48%), pericentral RP (5%) or sectoral RP (21%). Patients with NBWD were
younger than the others, however the diffrence was not significant. Systemic diseases
were reported exlusievely by patients with classic and sectoral RP (75 % and 56 %),
who were also oldest. In a subgroup of patients aged 40 years or more, patients with a
milder clinical signs (NBWD, sectoral RP) had significantly higher vitamin A
concentration than patients with greater structural impairment (classic RP, pericentral
RP) (median 3.0 vs 2.0 μmol/L, Mann-Whitney test, p < 0.05).
Conclusions: Contrary to the previous report, p.G90D also causes various forms of
retinal dystrophy (classic RP, sector RP and pericentral RP) in addition to rod
dysfunction (CSNB or NBWD). Such phenotypic variability is unusual even among
more than 200 variants in RHO, which is not characteristic of them. Serum vitamin A
concentration is a possible disease modifier, however studies on larger cohorts and
longer follow-up are needed to confirm this.