Mutations in the gene PDE6C encoding the catalytic subunit of the cone photoreceptor phosphodiesterase in patients with achromatopsia.

Biallelic PDE6C mutations are a known cause for rod monochromacy, better known as autosomal recessive achromatopsia (ACHM), and early-onset cone photoreceptor dysfunction. PDE6C encodes the catalytic α'-subunit of the cone photoreceptor phosphodiesterase, thereby constituting an essential part of the phototransduction cascade. Here, we present the results of a study comprising 176 genetically preselected patients who remained unsolved after Sanger sequencing of the most frequent genes accounting for ACHM, and were subsequently screened for exonic and splice site variants in PDE6C applying a targeted next generation sequencing approach.

Genetic heterogeneity and clinical outcome in a Swedish family with retinal degeneration caused by mutations in CRB1 and ABCA4 genes.

Genetic mechanisms underlying severe retinal dystrophy in a large Swedish family presenting two distinct phenotypes, Leber congenital amaurosis and Stargardt disease were investigated. In the family, four patients with Leber congenital amaurosis were homozygous for a novel c.2557C>T (p.

Novel mutations in CRB1 and ABCA4 genes cause Leber congenital amaurosis and Stargardt disease in a Swedish family.

This study aimed to identify genetic mechanisms underlying severe retinal degeneration in one large family from northern Sweden, members of which presented with early-onset autosomal recessive retinitis pigmentosa and juvenile macular dystrophy. The clinical records of affected family members were analysed retrospectively and ophthalmological and electrophysiological examinations were performed in selected cases. Mutation screening was initially performed with microarrays, interrogating known mutations in the genes associated with recessive retinitis pigmentosa, Leber congenital amaurosis and Stargardt disease.

Central retinal findings in Bothnia dystrophy caused by RLBP1 sequence variation.

Objective: To describe the central retinal findings early in the course of Bothnia dystrophy caused by the homozygous missense R234W sequence variation in the RLBP1 gene.

Methods: In 8 young patients with Bothnia dystrophy (aged 9-34 years), high- and low-contrast distance visual acuity and visual fields were measured with Humphrey central (24-2) threshold testing and Goldmann perimetry. Central retinal thickness was measured with optical coherence tomography.

Self-reported quality of life in patients with retinitis pigmentosa and maculopathy of Bothnia type.

Purpose: To assess vision-related quality-of-life subscales with objective measurements of visual function in patients affected with retinitis pigmentosa of Bothnia type (BD).

Methods: Forty-nine patients answered the NEI-VFQ-25 questionnaire. High- and low-contrast distance acuity (VA), near VA, and visual fields (VF) were measured.

Rod-cone dystrophy with maculopathy in genetic glutathione synthetase deficiency: a morphologic and electrophysiologic study.

Purpose: To describe the retinal findings in 2 young adults with glutathione synthetase (GS) deficiency, an autosomal-recessive inborn error of glutathione (GSH) metabolism.

Design: Report of 2 cases.

Participants: Binocular study in 2 affected siblings.

Breakpoint characterization of a novel approximately 59 kb genomic deletion on 19q13.42 in autosomal-dominant retinitis pigmentosa with incomplete penetrance.

The aim of this study was to identify and characterize the underlying molecular mechanisms in autosomal-dominant retinitis pigmentosa (adRP) with incomplete penetrance in two Swedish families. An extended genealogical study and haplotype analysis indicated a common origin. Mutation identification was carried out by multiplex ligation-dependent probe amplification (MLPA) and sequencing.

Carrier of R14W in carbonic anhydrase IV presents Bothnia dystrophy phenotype caused by two allelic mutations in RLBP1.

Purpose: Bothnia dystrophy (BD) is an autosomal recessive retinitis pigmentosa (arRP) associated with the c.700C>T mutation in the RLBP1 gene. Testing of patients with BD has revealed the c.

Effects of prolonged dark adaptation in patients with retinitis pigmentosa of Bothnia type: an electrophysiological study.

Bothnia dystrophy (BD) is a variant of recessive retinitis punctata albescens (RPA), caused by the missense mutation R233W in cellular retinaldehyde-binding protein (CRALBP), which is localized in the retinal pigment epithelium (RPE) and Müller cells of the retina. The purpose of this study was, by examining the electrophysiological responses of the retina, to evaluate the capacity of recovery of the whole retinal area and different cell types induced by extremely prolonged dark adaptation (DA) in BD disease and to gain further understanding of the pathogenesis of BD. Six young patients underwent bilateral full-field ERGs after 24 h of DA in one eye and standard DA in the fellow eye.

Mutation in the PYK2-binding domain of PITPNM3 causes autosomal dominant cone dystrophy (CORD5) in two Swedish families.

Autosomal dominant cone dystrophy (CORD5) (MIM 600977) is a rare disease predominantly affecting cone photoreceptors. Here we refine the CORD5 locus previously mapped to 17p13 from 27 to 14.3 cM and identified a missense mutation, Q626H in the phosphatidylinositol transfer (PIT) membrane-associated protein (PITPNM3) (MIM 608921) in two Swedish families.

Tinted contact lenses in Bothnia dystrophy.

Purpose: To determine whether tinted contact lenses can improve visual function in patients with Bothnia dystrophy (BD), a genetically defined retinal dystrophy with prolonged dark adaptation.

Methods: Twelve patients with BD were fitted with the same type of soft contact lenses tinted dark brown. Visual acuity (VA), contrast vision, near vision and visual fields were tested before and 1 month after contact lens fitting.

Associations between specific measures of vision and vision-related quality of life in patients with bothnia dystrophy, a defined type of retinitis pigmentosa.

Purpose: To assess the relationship between objective tests of visual function and vision-related quality of life in patients with Bothnia dystrophy (BD), a retinal dystrophy of retinitis pigmentosa type with progressive maculopathy.

Methods: Forty-nine patients were tested. Weighted distance logMAR visual acuity (WVA), weighted logMAR low contrast VA (WCS), and binocular visual field (VF) areas were calculated.

Retinal function in Bothnia dystrophy. An electrophysiological study.

Using prolonged dark adaptometry, standard dark adaptation (DA) and prolonged DA full-field electroretinograms (ERGs), we analysed the retinal function in patients with Bothnia dystrophy (BD), a variant of recessive retinitis punctata albescens (RPA). A compromised rod and cone function, a likely dysfunction of the Müller cells, and indications of disturbed neuronal function of the inner retina, were found. With prolonged DA, a gradual increase in retinal sensitivity to light and an improvement of the ERG components occurred.

Disease-causing mutations in the cellular retinaldehyde binding protein tighten and abolish ligand interactions.

Mutations in the human cellular retinaldehyde binding protein (CRALBP) gene cause retinal pathology. To understand the molecular basis of impaired CRALBP function, we have characterized human recombinant CRALBP containing the disease causing mutations R233W or M225K. Protein structures were verified by amino acid analysis and mass spectrometry, retinoid binding properties were evaluated by UV-visible and fluorescence spectroscopy and substrate carrier functions were assayed for recombinant 11-cis-retinol dehydrogenase (rRDH5).