Autosomal dominant retinitis pigmentosa in Norway: a 20‐year clinical follow‐up study with molecular genetic analysis. Two novel rhodopsin mutations: 1003delG and I179F

Abstract

Six of 12 families had an RHO mutation. The mutation V345M and the novel mutation 1003delG both caused classical RP, the former indicating the most unfavourable prognosis. Two of the families with PRD had the A164V mutation with a favourable prognosis, whereas the novel mutation I179F caused PRD with extremely variable expressivity.

Molecular Heterogeneity Within the Clinical Diagnosis of Pericentral Retinal Degeneration

“…11,12,17 Common to the three studies are data for visual acuities and ERGs. One study was mainly of simplex RP patients with a pericentral distribution of disease.…”

“…Five patients from ad pedigrees were screened for mutations in adRP-associated genes through the Carver Laboratory or with APEX microarrays (385 or 414 variants arrays; Asper Ophthalmics). Because the adRP arrays included mutations in RHO and TOPORS, genes previously reported in PRD patients, 12,17 and in RDS, which was causative in one pericentral patient, 33 simplex and multiplex patients who were negative on arRP panels were also screened on the adRP arrays. All patients without a molecular diagnosis were screened for mutations in ABCA4 with APEX microarrays (496, 519, or 577 variants arrays; Asper Ophthalmics), 34 by Carver Laboratory or by Casey Eye Institute Molecular Testing Laboratory (Portland, OR, USA).…”

“…One of the studies was the first to identify a molecular basis of the pericentral phenotype and two missense mutations in the RHO gene were found. 17 Visual acuities were 20/20 to 20/25 in at least one eye of 16 of 22 patients but were reduced in all others. Electroretinograms were listed in four patients and these were abnormal; most were recordable.…”

“…11,16 Some autosomal dominant (ad) Norwegian families with affected members showing a pericentral pattern of disease had missense mutations in the RHO (rhodopsin) or TOPORS (topoisomerase I-binding arginine/serine rich) genes. 12,17 We identified a cohort of RD patients with a pericentral pattern of disease and then studied their phenotype by measures of visual function and retinal imaging. Gene screening was performed and one-half of the patients were found to have mutations in genes previously associated with ad or ar retinal degenerations.…”

Intravitreal Injection of Autologous Bone Marrow–derived Mononuclear Cells for Hereditary Retinal Dystrophy

“…1 They are characterized by progressive visual field and visual acuity loss, night blindness, optic nerve atrophy, arteriolar attenuation, and altered vascular permeability, often progressing to complete blindness. 1 Molecular genetic analysis of these diseases has identified mutations in more than 110 different genes accounting for only a relatively small percentage of the known affected individuals 2,3 ; many of these mutations are associated with enzymatic and structural components of the phototransduction machinery, including rhodopsin, 4 cyclic guanosine monophosphate phosphodiesterase, 5 peripherin, 6,7 and RPE65. 8 Despite these observations, there are still no effective treatments to slow or reverse the progression of these dystrophies.…”