Mutation update: TGFBI pathogenic and likely pathogenic variants in corneal dystrophies.

Human transforming growth factor β-induced (TGFBI), is a gene responsible for various corneal dystrophies. TGFBI produces a protein called TGFBI, which is involved in cell adhesion and serves as a recognition sequence for integrins. An alteration in cell surface interactions could be the underlying cause for the progressive accumulation of extracellular deposits in different layers of the cornea with the resulting changes of refractive index and transparency.

Analysis of Gene Mutations in Three Chinese Families with Corneal Dystrophy.

Objective: To identify the types of (transforming growth factor, beta-induced) gene mutations in three Chinese families with Reis-Bücklers corneal dystrophy (RBCD), lattice corneal dystrophy type I (LCDI), or Avellino corneal dystrophy (ACD) and to investigate the relationship between the phenotypes and genotypes of corneal dystrophy.

Methods: Peripheral blood was collected from 24 patients and 76 phenotypically normal members in three Chinese families as well as from 100 healthy controls. Genomic DNA was extracted.

Characterization of neurite dystrophy after trauma by high speed structured illumination microscopy and lattice light sheet microscopy.

Background: Unbiased screening studies have repeatedly identified actin-related proteins as one of the families of proteins most influenced by neurotrauma. Nevertheless, the status quo model of cytoskeletal reorganization after neurotrauma excludes actin and incorporates only changes in microtubules and intermediate filaments. Actin is excluded in part because it is difficult to image with conventional techniques.

Dystrophin As a Molecular Shock Absorber.

Dystrophin is the largest protein isoform (427 kDa) expressed from the gene defective in Duchenne muscular dystrophy, a lethal muscle-wasting and genetically inherited disease. Dystrophin, localized within a cytoplasmic lattice termed costameres, connects the intracellular cytoskeleton of a myofiber through the cell membrane (sarcolemma) to the surrounding extracellular matrix. In spite of its mechanical regulation roles in stabilizing the sarcolemma during muscle contraction, the underlying molecular mechanism is still elusive.

Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging of Key Proteins in Corneal Samples from Lattice Dystrophy Patients with TGFBI-H626R and TGFBI-R124C Mutations.

Scope: The purpose of this study is to identify and visualize the spatial distribution of proteins present in amyloid corneal deposits of TGFBI-CD patients using Mass Spectrometry Imaging (MSI) and compare it with healthy control cornea. Corneal Dystrophies (CD) constitute a group of genetically inherited protein aggregation disorders that affects different layers of the cornea. With accumulated protein deposition, the cornea becomes opaque with decreased visual acuity.

[Analysis of TGFBI gene mutation in a Chinese pedigree affected with lattice corneal dystrophy].

Objective: To explore the clinical features and mutation of TGFBI gene in a Chinese pedigree affected with lattice corneal dystrophy (LCD).

Methods: Genomic DNA was extracted from 35 members including 11 patients from the pedigree. The 17 exons and splicing region of introns of the TGFBI gene were amplified by PCR.

Polymicrobial Keratitis With Cryptococcus curvatus, Candida parapsilosis, and Stenotrophomonas maltophilia After Penetrating Keratoplasty: A Rare Case Report With Literature Review.

Objectives: To report the first case of fungal keratitis caused by Cryptococcus curvatus after penetrating keratoplasty (PK) in an immunocompetent patient and to describe its therapeutic challenge and long-term outcome.

Methods: An interventional case report.

Results: A 54-year-old female patient underwent right PK for lattice dystrophy.

Prevalence of stromal corneal dystrophies in Lahore.

To determine the prevalence of Stromal Corneal Dystrophies (SCDs) in patient from Lahore hospitals. The study was performed between November, 2014 to July 2015 at the Layton Rahmatullah Benevolent Trust Hospital, Mughal Hospital, Mayo Hospital and General Hospital, Lahore. For the clinical evaluation of SCD by ophthalmologists examination of cornea was done by biomicroscopy, specular microscopy, topography, keratometry, orbscan and far visual acuity.

Cataract surgery after deep anterior lamellar keratoplasty and penetrating keratoplasty in age- and disease-matched eyes.

Purpose: To assess the efficacy and safety of cataract surgery after deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PKP).

Setting: Tokyo Dental College Ichikawa General Hospital, Chiba, Japan.

Design: Retrospective case series.

Outcomes of keratoplasty in lattice corneal dystrophy in a large cohort of Indian eyes.

Purpose: The purpose of this study is to evaluate the outcomes of keratoplasty for lattice corneal dystrophy (LCD) performed at a tertiary eye care center.

Methods: A retrospective review of medical records of those patients who were clinically diagnosed to have LCD (72 eyes of 57 patients) and underwent either penetrating keratoplasty (PK, 58 eyes of 46 patients) or deep anterior lamellar keratoplasty (DALK, 14 eyes of 13 patients) between the years 1987 and 2014 was performed. The main outcome measures included demographics, clinical features, and outcomes of keratoplasty.

[Limbokeratoplasty to Treat Lattice and Granular Corneal Dystrophies].

The surgical technique of limbokeratoplasty (limbo-KP) was initially established for the treatment of severe limbal deficiencies. Besides improving visual acuity, surgery is aimed at ensuring complete, long-lasting epithelialization of the ocular surface. Due to the extension of the indication spectrum, limbo-KPs are also used in various forms of epithelial/stromal corneal dystrophies such as lattice and granular (transforming growth factor beta-induced [TGFBI] gene mutation associated) dystrophies.

The Gelsolin Pathogenic D187N Mutant Exhibits Altered Conformational Stability and Forms Amyloidogenic Oligomers.

Gelsolin is an actin-severing protein that attains an open functional conformation in the presence of Ca or low pH. Mutations (D187N/Y) in the second domain of gelsolin trigger the proteolytic pathway producing amyloidogenic fragments that form the pathological hallmark of gelsolin amyloidosis and lattice corneal dystrophy type 2 (LCD2). Here, we show that the D187N mutant gelsolin in a Ca depleted, low pH-activated, open conformation could assemble into amyloidogenic oligomers without necessarily undergoing the specific proteolytic step.

Variable rescue of microtubule and physiological phenotypes in mdx muscle expressing different miniaturized dystrophins.

Delivery of miniaturized dystrophin genes via adeno-associated viral vectors is one leading approach in development to treat Duchenne muscular dystrophy. Here we directly compared the functionality of five mini- and micro-dystrophins via skeletal muscle-specific transgenic expression in dystrophin-deficient mdx mice. We evaluated their ability to rescue defects in the microtubule network, passive stiffness and contractility of skeletal muscle.

Atypical Presentation of Gelsolin Amyloidosis in a Man of African Descent with a Novel Mutation in the Gelsolin Gene.

BACKGROUND Gelsolin amyloidosis is a very rare systemic disease presenting with a pathognomonic triad of corneal lattice dystrophy, cutis laxa, and polyneuropathy. The disease is mostly restricted to a Finnish population with known mutations (G654A, G654T) in exon 4 of the gelsolin gene. The mutations lead to errors in protein processing and folding, and ultimately leads to deposition of an amyloidogenic fragment in the extracellular space, causing the symptoms of disease.

Transplantation Blues: Inadvertent Staining of Amyloid Deposits With Trypan Blue.

Purpose: To describe inadvertent persistent staining of stromal amyloid deposits by trypan blue (TB) after penetrating keratoplasty (PK) and Descemet membrane endothelial keratoplasty (DMEK) performed in patients with corneal amyloidosis.

Methods: Case series of patients with corneal amyloidosis in whom intraoperative TB was used.

Results: One patient, hospitalized for acute rejection 6 weeks after DMEK, presented with an intense blue staining of small, spindle-shaped structures in the anterior half of the cornea.

Lamins and Lamin-Associated Proteins in Gastrointestinal Health and Disease.

The nuclear lamina is a multi-protein lattice composed of A- and B-type lamins and their associated proteins. This protein lattice associates with heterochromatin and integral inner nuclear membrane proteins, providing links among the genome, nucleoskeleton, and cytoskeleton. In the 1990s, mutations in EMD and LMNA were linked to Emery-Dreifuss muscular dystrophy.

Corneal Dystrophy Mutations Drive Pathogenesis by Targeting TGFBIp Stability and Solubility in a Latent Amyloid-forming Domain.

Numerous mutations in the corneal protein TGFBIp lead to opaque extracellular deposits and corneal dystrophies (CDs). Here we elucidate the molecular origins underlying TGFBIp's mutation-induced increase in aggregation propensity through comprehensive biophysical and bioinformatic analyses of mutations associated with every major subtype of TGFBIp-linked CDs including lattice corneal dystrophy (LCD) and three subtypes of granular corneal dystrophy (GCD 1-3). LCD mutations at buried positions in the C-terminal Fas1-4 domain lead to decreased stability.

Altered myofilament structure and function in dogs with Duchenne muscular dystrophy cardiomyopathy.

Aim: Duchenne Muscular Dystrophy (DMD) is associated with progressive depressed left ventricular (LV) function. However, DMD effects on myofilament structure and function are poorly understood. Golden Retriever Muscular Dystrophy (GRMD) is a dog model of DMD recapitulating the human form of DMD.

Prevalence of transforming growth factor β-induced gene corneal dystrophies in Chinese refractive surgery candidates.

Purpose: To determine the prevalence of the transforming growth factor (TGF) β-induced gene corneal dystrophies in refractive surgery candidates in China.

Setting: Five hospitals in China.

Design: Prospective case series.

Transforming growth factor β induced mutation-associated phenotype in a Chinese family exhibiting lattice corneal dystrophy.

Lattice corneal dystrophy type I (LCDI) is associated with a large number of missense mutations in the transforming growth factor β induced () gene. The aim of the present study was to analyze mutation in a Chinese family with LCDI, and to describe the clinical features and phenotype-genotype correlation within this family. Three generations of this family with LCDI were enrolled in the current study.

The First Argentinian Family with Familial Amyloidosis of the Finnish Type.

Familial amyloidosis of the Finnish type or Meretoja syndrome is a rare autosomic dominant inherited systemic condition. It was first described by Meretoja in Finland in 1969. It is a disease produced by a single mutation in the gene coding for gelsolin, which generates an abnormal protein that cumulates in tissues and leads to various signs.

CaF nanoparticles as surface carriers of GCAP1, a calcium sensor protein involved in retinal dystrophies.

CaF-based nanoparticles (NP) are promising biocompatible tools for nanomedicine applications. The structure of the NP crystal lattice allows for specific interactions with Ca-binding proteins through their EF-hand cation binding motifs. Here we investigated the interaction of 23 nm citrate-coated CaF NP with a calcium sensor protein GCAP1 that is normally expressed in photoreceptor cells and involved in the regulation of the early steps of vision.