Premature Vertebral Mineralization in -Mutant Zebrafish.

H6 family homeobox 1 (HMX1) regulates multiple aspects of craniofacial development, and mutations in are linked to an ocular defect termed oculoauricular syndrome of Schorderet-Munier-Franceschetti (OAS) (MIM #612109). Recently, additional altered orofacial features have been reported, including short mandibular rami, asymmetry of the jaws, and altered premaxilla. We found that in two mutant zebrafish lines termed and , precocious mineralization of the proximal vertebrae occurred.

Different Phenotypes in Pseudodominant Inherited Retinal Dystrophies.

Retinal dystrophies (RD) are a group of Mendelian disorders caused by rare genetic variations leading to blindness. A pathogenic variant may manifest in both dominant or recessive mode and clinical and genetic heterogeneity makes it difficult to establish a precise diagnosis. In this study, families with autosomal dominant RD in successive generations were identified, and we aimed to determine the disease's molecular origin in these consanguineous families.

Hmx1 regulates urfh1 expression in the craniofacial region in zebrafish.

H6 family homeobox 1 (HMX1) regulates multiple aspects of craniofacial development as it is widely expressed in the eye, peripheral ganglia and branchial arches. Mutations in HMX1 are linked to an ocular defect termed Oculo-auricular syndrome of Schorderet-Munier-Franceschetti (MIM #612109). We identified UHRF1 as a target of HMX1 during development.

Genetic spectrum of retinal dystrophies in Tunisia.

We report the molecular basis of the largest Tunisian cohort with inherited retinal dystrophies (IRD) reported to date, identify disease-causing pathogenic variants and describe genotype-phenotype correlations. A subset of 26 families from a cohort of 73 families with clinical diagnosis of autosomal recessive IRD (AR-IRD) excluding Usher syndrome was analyzed by whole exome sequencing and autozygosity mapping. Causative pathogenic variants were identified in 50 families (68.

Correction: Habibi I. et al. "Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy (ARB)" Genes, 2019, , 953.

The authors wish to make a correction to the published version of their paper [...

Posterior staphylomas in non-highly myopic eyes with retinitis pigmentosa.

Purpose: Our aim was to highlight the presence and the frequency of posterior staphyloma (PS) in non-highly myopic retinitis pigmentosa (RP) patients and to study the relationship between PS and choroidal thickness (CT).

Methods: This was a retrospective case-control study of 77 eyes (39 patients) with RP, axial length inferior to 26 mm and clinically preserved macular area. All patients underwent fundus photography, A- and B-scan ocular ultrasonography, fundus autofluorescence (FAF) and swept source optical coherence tomography (SS-OCT).

Mutations in VSX2, SOX2, and FOXE3 Identified in Patients with Micro-/Anophthalmia.

Anophthalmia and microphthalmia (A/M) are rare distinct phenotypes that represent a continuum of structural developmental eye defects. Here, we describe three probands from an Egyptian population with various forms of A/M: two patients with bilateral anophthalmia and one with bilateral microphthalmia that were investigated using whole exome sequencing (WES). We identified three causative mutations in three different genes.

Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy (ARB).

Mutations in cause several phenotypes including autosomal dominant (AD) Best vitelliform macular dystrophy type 2 (BVMD), AD vitreo-retino-choroidopathy (ADVIRC), and retinitis pigmentosa-50 (RP50). A rare subtype of Bestrophinopathy exists with biallelic mutations in . Its frequency is estimated to be 1/1,000,000 individuals.

Where are the missing gene defects in inherited retinal disorders? Intronic and synonymous variants contribute at least to 4% of CACNA1F-mediated inherited retinal disorders.

Inherited retinal disorders (IRD) represent clinically and genetically heterogeneous diseases. To date, pathogenic variants have been identified in ~260 genes. Albeit that many genes are implicated in IRD, for 30-50% of the cases, the gene defect is unknown.

CRX-linked macular dystrophy with intrafamilial variable expressivity.

Background: We present a macular dystrophy of differing severity in a single kindred caused by a heterozygous nonsense mutation in CRX.

Case Report: A 21-year-old Caucasian male from a Swiss family was investigated for decreasing central visual acuity associated with dischromatopsia. Clinical examination revealed posterior pole atrophy, including the maculopapillary bundle.

Higher retinal vessel oxygen saturation: investigating its relationship with macular oedema in retinitis pigmentosa patients.

Purpose: Primary objective-to investigate the effect of retinal vessel oxygen saturation (SO) on macular oedema (ME) in retinitis pigmentosa (RP) patients. Secondary objective-to link the presence of ME to metabolic (oxygen saturation of retinal vessels, SO), functional (multifocal electroretinography, mfERG) and structural (Spectral Domain Optical Coherent Tomography, SD-OCT) alterations in RP.

Design: Prospective, cross-sectional, non-interventional study.

Prominent Optic Disc Featured in Inherited Retinopathy.

We investigated the relationship between prominent optic disc (POD) and inherited retinal dystrophy (IRD). A cross-sectional consecutive study was performed in 10 children and 11 adults of 7 non-related families. We performed clinical phenotyping, including a detailed examination, fundus autofluorescence, and colour fundus and OCT imaging.

Bigh3 silencing increases retinoblastoma tumor growth in the murine SV40-TAg-Rb model.

BIGH3, a secreted protein of the extracellular matrix interacts with collagen and integrins on the cell surface. BIGH3 can have opposing functions in cancer, acting either as tumor suppressor or promoter by enhancing tumor progression and angiogenesis. In the eye, BIGH3 is expressed in the cornea and the retinal pigment epithelium and could impact on the development of retinoblastoma, the most common paediatric intraocular neoplasm.

Reduced metabolic function and structural alterations in inherited retinal dystrophies: investigating the effect of peripapillary vessel oxygen saturation and vascular diameter on the retinal nerve fibre layer thickness.

Purpose: To evaluate the relationship between the peripapillary metabolic alterations [retinal vessel Oximetry (RO)] and the structural findings [retinal vessel diameter and retinal nerve fibre layer thickness (RNFL)] in patients with inherited retinal dystrophies (IRD).

Methods: Patients with IRD [24 patients with rod-cone dystrophy (RCD), 15 patients with cone-rod dystrophy, 13 patients with inherited maculopathy] and 18 age-matched controls, who underwent RO imaging and spectral domain optical coherence tomography, were included. The average and quadrant oxygen saturation in all four major peripapillary retinal arterioles (A-SO ) and venules (V-SO ) were measured, and their difference (A-V SO ) was calculated.

Preserved functional and structural integrity of the papillomacular area correlates with better visual acuity in retinitis pigmentosa.

PurposeLinking multifocal electroretinography (mfERG) and optical coherence tomography (OCT) findings with visual acuity in retinitis pigmentosa (RP) patients.DesignProspective, cross-sectional, nonintervention study.SubjectsPatients with typical RP and age-matched controls, who underwent SD-OCT (spectral domain OCT) and mfERG, were included.

A Novel Recessive RPGRIP1 Mutation Causing Leber Congenital Amaurosis.

Background: Leber congenital amaurosis is an early-onset childhood severe retinal dystrophy, of significant genetic heterogeneity. RPGRIP1 is ubiquitously expressed, but mutations in RPGRIP1 lead to a retina-restricted phenotype, such as Leber congenital amaurosis and cone-rod dystrophy.

Patient And Methods: We analysed a consanguineous family from Egypt in which one individual, a four-year-old girl, was affected with Leber congenital amaurosis.

Metabolic and functional changes in retinitis pigmentosa: comparing retinal vessel oximetry to full-field electroretinography, electrooculogram and multifocal electroretinography.

Purpose: To determine a relationship between the retinal vessel saturation alterations and the residual retinal function measured by means of full-field electroretinography (full-field ERG), electrooculogram (EOG) and multifocal electroretinography (mfERG) in patients with retinitis pigmentosa (RP).

Methods: Retinal vessel oximetry (RO), full-field ERG, EOG and mfERG were performed on 43 eyes of 22 patients suffering from RP and were compared to those of 26 eyes of 13 healthy controls. The oxygen saturation in the first and second branch retinal arterioles (A-SO2 ) and venules (V-SO2 ) was measured, and their difference (A-V SO2 ) was calculated.

JNK Inhibition Reduced Retinal Ganglion Cell Death after Ischemia/Reperfusion In Vivo and after Hypoxia In Vitro.

Mitogen-activated protein kinases (MAPKs) are key regulators that have been linked to cell survival and death. Among the main classes of MAPKs, c-jun N-terminal kinase (JNK) has been shown to mediate cell stress responses associated with apoptosis. In Vitro, hypoxia induced a significant increase in 661W cell death that paralleled increased activity of JNK and c-jun.

Corneal Dystrophies: Overview and Summary.

In this chapter, I shall discuss the genetics, mode of inheritance and molecular origin of several corneal dystrophies.

Potential blindness in children of patients with hereditary bone disease.

Mono- and bi-allelic mutations in the low-density lipoprotein receptor related protein 5 (LRP5) may cause osteopetrosis, autosomal dominant and recessive exudative vitreoretinopathy, juvenile osteoporosis, or persistent hyperplastic primary vitreous (PHPV). We report on a child affected with PHPV and carrying compound mutations. The father carried the splice mutation and suffered from severe bone fragility since childhood.

Molecular Analysis of NOTCH2 in Patients with Primary Open-Angle Glaucoma.

Background And Purpose: Transgenic mice overexpressing Notch2 in the uvea exhibit a hyperplastic ciliary body leading to increased IOP and glaucoma. The aim of this study was to investigate the possible presence of NOTCH2 variants in patients with primary open-angle glaucoma (POAG).

Methods: We screened DNA samples from 130 patients with POAG for NOTCH2 variants by denaturing high-performance liquid chromatography after PCR amplification and validated our data by direct Sanger sequencing.

Differential dimerization of variants linked to enhanced S-cone sensitivity syndrome (ESCS) located in the NR2E3 ligand-binding domain.

NR2E3 encodes the photoreceptor-specific nuclear hormone receptor that acts as a repressor of cone-specific gene expression in rod photoreceptors, and as an activator of several rod-specific genes. Recessive variants located in the ligand-binding domain (LBD) of NR2E3 cause enhanced short wavelength sensitive- (S-) cone syndrome (ESCS), a retinal degeneration characterized by an excess of S-cones and non-functional rods. We analyzed the dimerization properties of NR2E3 and the effect of disease-causing LBD missense variants by bioluminescence resonance energy transfer (BRET(2) ) protein interaction assays.

Novel ADAM9 homozygous mutation in a consanguineous Egyptian family with severe cone-rod dystrophy and cataract.

Objective: To genetically and phenotypically describe a new ADAM9 homozygous mutation in a consanguineous family from Egypt with autosomal recessive cone-rod dystrophy (arCRD), anterior polar and posterior subcapsular cataract.

Design, Setting And Participants: The parents and their six children were included. They underwent a complete ophthalmic examination with fundus photography and optical coherence tomography (OCT).

A dimerized HMX1 inhibits EPHA6/epha4b in mouse and zebrafish retinas.

HMX1 is a homeobox-containing transcription factor implicated in eye development and responsible for the oculo-auricular syndrome of Schorderet-Munier-Franceschetti. HMX1 is composed of two exons with three conserved domains in exon 2, a homeobox and two domains called SD1 and SD2. The function of the latter two domains remains unknown.