transforming-growth-factor-beta and Diseases-in-Twins

To report a de novo R124C mutation of transforming growth factor β-induced (TGFBI) gene in one of dizygotic twins with corneal dystrophy of the Bowman layer.. An 11-year-old boy was one of dizygotic twins and had a history of bilateral blurred vision and recurrent corneal erosion. Examination of the visual acuity demonstrated 20/40 in his each eye. Biomicroscopy showed bilaterally central corneal subepithelial opacities and some dot opacities in the superficial stroma. Anterior segment optical coherence tomography demonstrated most hyperreflective opacities at the subepithelial layer with some interspersed opacities in the superficial stroma. Confocal microscopy revealed irregular hyperreflective materials in the Bowman layer and the superficial stroma. Several rough filaments were found in the middle layer of stroma, corresponding to a feature of amyloid lattice. The corneas of his parents and dizygotic sister were clear. Sequencing of the TGFBI gene revealed an R124C mutation in the affected boy but not in his three healthy family members.. A de novo R124C mutation of the TGFBI gene may occur in one of dizygotic twins. Patients with an R124C mutation may have clinical features like corneal dystrophy of the Bowman layer. Confocal microscopy can be used to detect subclinical lattice lines, thereby facilitating differential diagnosis.

Topics: Bowman Membrane; Child; Corneal Dystrophies, Hereditary; Diseases in Twins; DNA Mutational Analysis; Exons; Extracellular Matrix Proteins; Female; Humans; Male; Microscopy, Confocal; Mutation; Pedigree; Tomography, Optical Coherence; Transforming Growth Factor beta; Twins, Dizygotic; Visual Acuity

Clinical studies suggest metabolic memory to hyperglycemia. We tested whether diabetes leads to persistent systematic in vitro gene expression alterations in patients with type 1 diabetes (T1D) compared with their monozygotic, nondiabetic twins. Microarray gene expression was determined in skin fibroblasts (SFs) of five twin pairs cultured in high glucose (HG) for ∼6 weeks. The Exploratory Visual Analysis System tested group differences in gene expression levels within KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. An overabundance of differentially expressed genes was found in eight pathways: arachidonic acid metabolism (P = 0.003849), transforming growth factor-β signaling (P = 0.009167), glutathione metabolism (P = 0.01281), glycosylphosphatidylinositol anchor (P = 0.01949), adherens junction (P = 0.03134), dorsal-ventral axis formation (P = 0.03695), proteasome (P = 0.04327), and complement and coagulation cascade (P = 0.04666). Several genes involved in epigenetic mechanisms were also differentially expressed. All differentially expressed pathways and all the epigenetically relevant differentially expressed genes have previously been related to HG in vitro or to diabetes and its complications in animal and human studies. However, this is the first in vitro study demonstrating diabetes-relevant gene expression differences between T1D-discordant identical twins. These SF gene expression differences, persistent despite the HG in vitro conditions, likely reflect "metabolic memory", and discordant identical twins thus represent an excellent model for studying diabetic epigenetic processes in humans.

Topics: Adult; Arachidonic Acid; Capillary Permeability; Cells, Cultured; Diabetes Mellitus, Type 1; Diseases in Twins; Female; Fibroblasts; Gene Expression Profiling; Glutathione; Humans; Male; Middle Aged; Signal Transduction; Skin; Transforming Growth Factor beta; Twins, Monozygotic

Topics: Amino Acid Substitution; Diseases in Twins; Genetic Predisposition to Disease; Humans; Immunity, Innate; Inflammatory Bowel Diseases; Interleukin-17; Interleukin-6; Mutation, Missense; Receptors, Interleukin; T-Lymphocytes, Helper-Inducer; Transforming Growth Factor beta

Osteoporosis is a disease affecting mainly women but also an increasing number of men. The destruction of the bone microarchitecture and the reduction of bone mass lead to increased fragility and pathologic bone fractures. Family studies and twin studies have shown that peak bone mass, mechanical strength, and physiological bone turnover are subject to genetic control. Vitamin D receptor polymorphisms were one of the first genetic factors suggested to influence bone phenotype, although their impact on bone metabolism was initially overestimated. Meanwhile, polymorphisms in numerous other genes such as collagen I alpha 1, estrogen receptor, transforming growth factor beta (TGF-beta), interleukin-1, interleukin-6, calcitonin, parathyroid hormone, and apolipoprotein E have been found to be associated with bone mineral density. In the interpretation of genetic findings, genetic differences between different ethnic groups, environmental factors such as calcium intake, vitamin D status, hormonal status, body size, and total body bone mineral density have to be considered. Understanding the molecular physiology of the genes described in this article and all genes influencing bone metabolism identified in the future will enable us to identify persons at risk for osteoporosis and to develop more specific therapies.

Topics: Apolipoproteins A; Bone and Bones; Bone Density; Calcitonin; Collagen; Diagnosis, Differential; Diseases in Twins; Female; Genotype; Humans; Interleukin-1; Interleukin-6; Male; Osteoporosis; Parathyroid Hormone; Phenotype; Polymorphism, Genetic; Receptors, Calcitriol; Receptors, Estrogen; Sex Factors; Transforming Growth Factor beta

Topics: Activins; Animals; Chickens; Diseases in Twins; Embryonic Induction; Hedgehog Proteins; Humans; Inhibins; Nodal Protein; Proteins; Trans-Activators; Transforming Growth Factor beta; Twins, Conjoined