![]() Orchiopexy was performed at 2-3 years because of his undescended testis. Block appearance was detected in the cervical vertebrae. His neurological development was retarded. Inner and outer ear anomalies and mixed hearing loss were present. He was operated because of vascular ring compression on his esophagus. Objective: Here, a case of CHARGE syndrome, which had no ocular coloboma and choanal atresia findings but had other features and was diagnosed genetically at a late age, was discussed.Ĭase: The 20-year-old male patient who had no problems during delivery had recurrent pneumonias. The disease has four major findings expressed as 4C ocular coloboma, choanal atresia, cranial nerve abnormalities, and characteristic ear anomalies. The name reflects the initials of the clinical findings (Coloboma, Heart disease, Atresia of the choanae, Retarded growth and mental development, Genital anomalies, Ear malformations, and hearing loss). Chapter 5 is a discussion of conclusions from these studies and how these findings lead to future work connecting Chd7 and Sox11 with retinal development and CHARGE syndrome.Background: CHARGE Syndrome is a rare inherited congenital disorder. Chapter 4 describes the process to establish mutant lines for both co-orthologues of Sox11, sox11a and sox11b, and the beginning characterization of retinal phenotypes in sox11 mutants. Chapter 3 describes the development of a transgenic zebrafish line in which Sox11a carries an in-frame epitope tag, which will allow for further study of Sox11a expression and provides a tool for identification of its transcriptional targets. Using two different mutant zebrafish lines for Chd7, this work demonstrates that there is a role for Chd7 in retinal neurogenesis and uncovers a novel role for Chd7 in photoreceptor maintenance. Chapter 2 focuses on characterizing the expression of Chd7 in the developing retina of two animal models. However, the connection between Chd7 and Sox11 in retinal development is still relatively unexplored.Ĭhapter 1 of this dissertation is a review of eye development with a focus on retinal development, the ocular defects of CHARGE syndrome, and what is known about the functions of Chd7 and Sox11. Knockdown of Sox11 in zebrafish results in microphthalmia, coloboma, brain, trunk, and heart defects, all phenotypes observed in CHARGE syndrome. The second gene of interest, Sox11, is a member of the SoxC family of transcription factors and has been shown to be a downstream target of CHD7 in brain neurogenesis. ![]() CHD7, a member of the CHD family of ATP-dependent chromatin remodelers, has been shown to have a role in neurogenesis in several different areas of the nervous system including the brain, spinal cord, auditory, and olfactory structures however, little is known about its role in retinal development. The different retinal cell types are generated in a conserved temporal order and lead to construction of the structures allowing for phototransduction. The neural retina is formed from the inner layer of the optic cup, and the single pool of retinal progenitor cells ultimately differentiates into six different neuronal classes and the Müller glia. This work focuses on investigating and developing tools to better understand the function of Chd7 and Sox11 in retinal development and photoreceptor maintenance, and how loss of expression causes the ocular phenotypes observed in CHARGE syndrome. Further work is needed to understand the developmental pathways that control oculogenesis and retinal neurogenesis, and to uncover the mechanism leading to the clinical phenotypes observed in CHARGE. Pathogenic variants in CHD7 have been identified as the most common genetic cause of CHARGE syndrome, however the mechanistic details of how these pathogenic variants result in ocular defects are poorly understood. One example is CHARGE syndrome, a genetic disorder characterized by coloboma, heart defects, choanal atresia, growth retardation, genital abnormalities, and ear abnormalities. Ocular developmental defects are often present in larger syndromic disorders. When this process is disrupted structural birth defects such as coloboma result, leading to pediatric visual deficits. Proper formation of the visual system requires the precise interaction of several embryonic cell lineages, including the neuroectoderm (forms the retina and retinal pigment epithelium), surface ectoderm (forms the lens), mesoderm and cranial neural crest cells (form the ocular blood vessels and anterior ocular structures).
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