Knockdown of Dehydrodolichyl Diphosphate Synthase in the Retina Leads to a Unique Pattern of Retinal Degeneration.

Dehydrodolichyl diphosphate synthase (DHDDS) is a ubiquitously expressed enzyme that catalyzes -prenyl chain elongation to produce the poly-prenyl backbone of dolichol. It appears in all tissues including the nervous system and it is a highly conserved enzyme that can be found in all animal species. Individuals who have biallelic missense mutations in the gene are presented with non-syndromic retinitis pigmentosa with unknown underlying mechanism.

Identification of genomic deletions causing inherited retinal degenerations by coverage analysis of whole exome sequencing data.

Background: Inherited retinal degenerations (IRDs) are a common cause of visual disturbance with a high clinical and genetic heterogeneity. Recent sequencing techniques such as whole exome sequencing (WES) contribute to the discovery of novel genes. The aim of the current study was to use WES data to identify large deletions that include at least one exon in known IRD genes.

Whole Exome Sequencing Reveals Mutations in Known Retinal Disease Genes in 33 out of 68 Israeli Families with Inherited Retinopathies.

Whole exome sequencing (WES) is a powerful technique for identifying sequence changes in the human genome. The goal of this study was to delineate the genetic defects in patients with inherited retinal diseases (IRDs) using WES. WES was performed on 90 patient DNA samples from 68 families and 226 known genes for IRDs were analyzed.

Association between missense mutations in the BBS2 gene and nonsyndromic retinitis pigmentosa.

Importance: A large number of genes can cause inherited retinal degenerations when mutated. It is important to identify the cause of disease for a better disease prognosis and a possible gene-specific therapeutic intervention.

Objective: To identify the cause of disease in families with nonsyndromic retinitis pigmentosa.

Whole exome sequencing reveals GUCY2D as a major gene associated with cone and cone-rod dystrophy in Israel.

Purpose: The Israeli population has a unique genetic make-up, with a high prevalence of consanguineous marriages and autosomal recessive diseases. In rod-dominated phenotypes, disease-causing genes and mutations that differ from those identified in other populations often are incurred. We used whole exome sequencing (WES) to identify genetic defects in Israeli families with cone-dominated retinal phenotypes.

A homozygous nonsense CEP250 mutation combined with a heterozygous nonsense C2orf71 mutation is associated with atypical Usher syndrome.

Background: Usher syndrome (USH) is a heterogeneous group of inherited retinitis pigmentosa (RP) and sensorineural hearing loss (SNHL) caused by mutations in at least 12 genes. Our aim is to identify additional USH-related genes.

Methods: Clinical examination included visual acuity test, funduscopy and electroretinography.

Ocular phenotype analysis of a family with biallelic mutations in the BEST1 gene.

Purpose: To investigate the genetic cause and perform a comprehensive clinical analysis of a Danish family with autosomal recessive bestrophinopathy; to investigate whether Bestrophin may be expressed in normal human retina.

Design: Retrospective clinical and molecular genetic analysis and immunohistochemical observational study.

Methods: setting: National referral center.

BBS1 mutations in a wide spectrum of phenotypes ranging from nonsyndromic retinitis pigmentosa to Bardet-Biedl syndrome.

Objective: To investigate the involvement of the Bardet-Biedl syndrome (BBS) gene BBS1 p.M390R variant in nonsyndromic autosomal recessive retinitis pigmentosa (RP).

Methods: Homozygosity mapping of a patient with isolated RP was followed by BBS1 sequence analysis.

The effect of cone opsin mutations on retinal structure and the integrity of the photoreceptor mosaic.

Purpose: To evaluate retinal structure and photoreceptor mosaic integrity in subjects with OPN1LW and OPN1MW mutations.

Methods: Eleven subjects were recruited, eight of whom have been previously described. Cone and rod density was measured using images of the photoreceptor mosaic obtained from an adaptive optics scanning light ophthalmoscope (AOSLO).

Frequency, genotype, and clinical spectrum of best vitelliform macular dystrophy: data from a national center in Denmark.

Purpose: To estimate the prevalence, genotype, and clinical spectrum of Best vitelliform macular dystrophy (Best disease).

Design: Retrospective epidemiologic and clinical and molecular genetic observational study.

Methods: setting: National referral center.

A tapetal-like fundus reflex in a healthy male: evidence against a role in the pathophysiology of retinal degeneration?

Purpose: To report on the retinal function and structure in a 37-year-old male who presented with a tapetal-like reflex (TLR) indistinguishable from that seen in female carriers of X-linked retinitis pigmentosa (XLRP).

Methods: Clinical examination included dark adaptometry, full-field electroretinography (ERG), multifocal ERG, optical coherence tomography, and fundus autofluorescence photography. Molecular genetic testing included screening for known mutations in autosomal dominant, autosomal recessive, and X linked retinitis pigmentosa (RP) genes with a commercially available chip, and sequencing analysis of retinitis pigmentosa GTPase regulator (RPGR)-open reading frame 15 (ORF15).

Enhanced S-cone function with preserved rod function: a new clinical phenotype.

Purpose: To describe the clinical findings and genetic analysis in two brothers having a novel retinal disease characterized by an enhanced S-cone phenotype with normal rod function.

Methods: Both patients underwent complete ophthalmologic examinations, including fundus photography, electroretinography (ERG), fluorescein angiography and optical coherence tomography (OCT). Mutation analysis of the following candidate genes was performed: nuclear receptor subfamily 2 group E member 3 (NR2E3), neural retina leucine zipper (NRL), nuclear receptor subfamily 1 group D member 1 (NR1D1), and thyroid hormone receptor beta (THRB).

A homozygous frameshift mutation in BEST1 causes the classical form of Best disease in an autosomal recessive mode.

Purpose: Best disease is a monogenic macular degeneration caused mainly by heterozygous mutations in the BEST1 gene. The objective was to characterize the molecular and clinical features of patients with the classical form of Best disease that is inherited in an autosomal recessive mode.

Methods: Clinical evaluation included detailed family history, a full ophthalmologic examination, electro-oculography (EOG), electroretinography, color vision testing, and ocular imaging.

A missense mutation in DHDDS, encoding dehydrodolichyl diphosphate synthase, is associated with autosomal-recessive retinitis pigmentosa in Ashkenazi Jews.

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerations caused by mutations in at least 50 genes. Using homozygosity mapping in Ashkenazi Jewish (AJ) patients with autosomal-recessive RP (arRP), we identified a shared 1.7 Mb homozygous region on chromosome 1p36.

Homozygosity mapping reveals null mutations in FAM161A as a cause of autosomal-recessive retinitis pigmentosa.

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerations caused by mutations in at least 45 genes. Using homozygosity mapping, we identified a ∼4 Mb homozygous region on chromosome 2p15 in patients with autosomal-recessive RP (arRP). This region partially overlaps with RP28, a previously identified arRP locus.

Variable retinal phenotypes caused by mutations in the X-linked photopigment gene array.

Purpose: To examine the involvement of the long (L) and middle (M) wavelength-sensitive cone opsin genes in cone-dominated phenotypes.

Methods: Clinical and molecular analyses included family history, color vision testing, full-field electroretinography (ERG), linkage analysis, and mutation detection.

Results: Eighteen families were recruited that had X-linked retinal disease characterized by cone impairment in which affected males usually had nystagmus, reduced visual acuity, normal to subnormal rod ERG, and reduced or extinguished cone ERG responses.

Prenatal molecular diagnosis of oculocutaneous albinism (OCA) in a large cohort of Israeli families.

Objectives: To present our accumulated data on prenatal molecular diagnosis of oculocutaneous albinism (OCA) in a large cohort of Israeli albino families.

Methods: Albinism consists of variable phenotypes, but only families with predicted severely handicapped albino offspring, who declared their wish to terminate a pregnancy of such a fetus, are eligible for prenatal testing. Prenatal testing is not offered otherwise.

Homozygosity for a novel ABCA4 founder splicing mutation is associated with progressive and severe Stargardt-like disease.

Purpose: To clinically characterize and genetically analyze members of six families who reside in the same village and manifest a rare form of retinal degeneration.

Methods: Ophthalmic evaluation included a full clinical examination, perimetry, color vision testing, and electroretinography. Genomic DNA was screened for ABCA4 mutations with the use of microarray analysis and direct sequencing.

A non-ancestral RPGR missense mutation in families with either recessive or semi-dominant X-linked retinitis pigmentosa.

Most X-linked diseases show a recessive pattern of inheritance in which female carriers are unaffected. In X-linked retinitis pigmentosa (XLRP), however, both recessive and semi-dominant inheritance patterns have been reported. We identified an Israeli family with semi-dominant XLRP due to a missense mutation (p.