Chromatin remodeler Chd7 regulates photoreceptor development and outer segment length.

Mutations in the chromatin remodeling factor CHD7 are the predominant cause of CHARGE syndrome, a congenital disorder that frequently includes ocular coloboma. Although CHD7 is known to be required for proper ocular morphogenesis, its role in retinal development has not been thoroughly investigated. Given that individuals with CHARGE syndrome can experience visual impairment even in the absence of coloboma, a better understanding of CHD7 function in the retina is needed.

Eyes on CHARGE syndrome: Roles of CHD7 in ocular development.

The development of the vertebrate visual system involves complex morphogenetic interactions of cells derived from multiple embryonic lineages. Disruptions in this process are associated with structural birth defects such as microphthalmia, anophthalmia, and coloboma (collectively referred to as MAC), and inherited retinal degenerative diseases such as retinitis pigmentosa and allied dystrophies. MAC and retinal degeneration are also observed in systemic congenital malformation syndromes.

Generation of a zebrafish knock-in line expressing MYC-tagged Sox11a using CRISPR/Cas9 genome editing.

Advances in CRISPR-Cas9 genome editing technology have strengthened the role of zebrafish as a model organism for genetics and developmental biology. These tools have led to a significant increase in the production of loss-of-function mutant zebrafish lines. However, the generation of precisely edited knock-in lines has remained a significant challenge in the field due to the decreased efficiency of homology directed repair (HDR).

Variable Anterior Segment Dysgenesis and Cardiac Anomalies Caused by a Novel Truncating Variant of FOXC1.

Anterior segment dysgenesis (ASD) encompasses a wide spectrum of developmental abnormalities of the anterior ocular segment, including congenital cataract, iris hypoplasia, aniridia, iridocorneal synechiae, as well as Peters, Axenfeld, and Rieger anomalies. Here, we report a large five-generation Caucasian family exhibiting atypical syndromic ASD segregating with a novel truncating variant of . The family history is consistent with highly variable autosomal dominant symptoms including isolated glaucoma, iris hypoplasia, aniridia, cataract, hypothyroidism, and congenital heart anomalies.

Author Correction: Her9/Hes4 is required for retinal photoreceptor development, maintenance, and survival.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Her9/Hes4 is required for retinal photoreceptor development, maintenance, and survival.

The intrinsic and extrinsic factors that regulate vertebrate photoreceptor specification and differentiation are complex, and our understanding of all the players is far from complete. Her9, the zebrafish ortholog of human HES4, is a basic helix-loop-helix-orange transcriptional repressor that regulates neurogenesis in several developmental contexts. We have previously shown that her9 is upregulated during chronic rod photoreceptor degeneration and regeneration in adult zebrafish, but little is known about the role of her9 during retinal development.

A new frontonasal dysplasia syndrome associated with deletion of the SIX2 gene.

The frontonasal dysplasias are a group of craniofacial phenotypes characterized by hypertelorism, nasal clefting, frontal bossing, and abnormal hairline. These conditions are caused by recessive mutations in members of the aristaless gene family, resulting in abnormal cranial neural crest migration and differentiation. We report a family with a dominantly inherited craniofacial phenotype comprised of frontal bossing with high hairline, ptosis, hypertelorism, broad nasal tip, large anterior fontanelle, cranial base anomalies, and sagittal synostosis.

Nucleoside Reverse Transcriptase Inhibitors Suppress Laser-Induced Choroidal Neovascularization in Mice.

Purpose: To evaluate the efficacy of nucleoside reverse transcriptase inhibitors (NRTIs) in the laser-induced mouse model of choroidal neovascularization (CNV).

Methods: We evaluated the NRTIs lamivudine (3TC), zidovudine (AZT), and abacavir (ABC) and the P2X7 antagonist A438079. Choroidal neovascularization was induced by laser injury in C57BL/6J wild-type, Nlrp3-/-, and P2rx7-/- mice, and CNV volume was measured after 7 days by confocal microscopy.

Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder.

Dominant optic atrophy (DOA) and axonal peripheral neuropathy (Charcot-Marie-Tooth type 2, or CMT2) are hereditary neurodegenerative disorders most commonly caused by mutations in the canonical mitochondrial fusion genes OPA1 and MFN2, respectively. In yeast, homologs of OPA1 (Mgm1) and MFN2 (Fzo1) work in concert with Ugo1, for which no human equivalent has been identified thus far. By whole-exome sequencing of patients with optic atrophy and CMT2, we identified four families with recessive mutations in SLC25A46.

Neuropathy target esterase impairments cause Oliver-McFarlane and Laurence-Moon syndromes.

Background: Oliver-McFarlane syndrome is characterised by trichomegaly, congenital hypopituitarism and retinal degeneration with choroidal atrophy. Laurence-Moon syndrome presents similarly, though with progressive spinocerebellar ataxia and spastic paraplegia and without trichomegaly. Both recessively inherited disorders have no known genetic cause.