27 research outputs found
Handbook of ocular genetics
No full textIncludes bibliographical references and index"Many serious, potentially blinding eye disorders have a genetic basis. Currently, there are relatively few ocular geneticists in the world, yet inherited eye disease is one of the leading causes of blindness worldwide. Significant strides have been made in gene identification and acquisition of knowledge on the underlying mechanisms of hereditary eye disease. The field of ocular genetics is becoming an increasingly relevant part of ophthalmologists'purview. This has resulted in a dire need for a comprehensive textbook ophthalmologists and other professionals who work with patients with genetic disorders can utilize to gain a better understanding of inherited eye disorders.The Wills Eye Handbook of Ocular Genetics, by Alex Levin, Mario Zanolli, and Jenina Capasso of Wills Eye Hospital, is a practical, reader-friendly guide on the diagnosis and management of ophthalmic genetic conditions. Every chapter begins with a disease overview, followed by relevant modern genetic concepts, pathways to attaining the correct diagnosis, and pitfalls and pearls gleaned from years of hands-on expertise. At the end of each chapter, questions and answers enable readers to test their knowledge in real-life scenarios they might face in everyday practice. The ultimate goal of this clinically robust handbook is to facilitate optimal patient management and outcomes.Key FeaturesFundamentals, including basic genetics, inheritance patterns, genetic testing, and ethical issuesPatient-centered genetic counseling issues such as reproduction, dealing with emotional reactions, prognosis, and future optionsAnterior segment disorders - from corneal dystrophies and aniridia - to childhood cataract and microphthalmiaA broad spectrum of vitreoretinopathies and retinal diseases including incontinentia pigmenti, retinitis pigmentosa, Bardet-Biedl syndrome, choroideremia, Stargardt disease, achromatopsia, and juvenile X-linked retinoschisisThis textbook is essential reading for practitioners at all levels and in all subspecialties including ophthalmology and genetics. They will find it an excellent resource for navigating the complexities of genetic eye disease."--Publisher.Basic Genetics -- Inheritance Patterns -- Genetic Testing -- Ethical Issues -- Corneal Dystrophies - Aniridia -- Peters Anomaly -- Axenfeld-Rieger Syndrome -- Primary Congenital Glaucoma and Juvenile Open Angle Glaucoma -- Childhood Cataract - Microphthalmia -- Marfan Syndrome and Other Causes of Ectopia Lentis -- Familial Exudative Vitreoretinopathy -- Stickler Syndrome -- VCAN Vitreoretinopathies (Erosive Vitreoretinopathy and Wagner Syndrome) -- Incontinentia Pigmenti -- Retinitis Pigmentosa -- Usher Syndrome -- Bardet-Biedl Syndrome -- Cone-Rod Dystrophy - Choroideremia -- Enhanced S-Cone Syndrome and Other NR2E3-Related Retinal Dystrophies -- Stargardt Disease and Other ABCA4 Retinopathies -- Best Vitelliform Macular Dystrophy (Best Disease) -- Leber Congenital Amaurosis - Achromatopsia -- Congenital Stationary Night Blindness -- Juvenile X-Linked Retinoschisis - Retinoblastoma -- Optic Nerve Hypoplasia -- Leber Hereditary Optic Neuropathy -- Complex Ocular Disorders - Albinism.1 online resource
Genetics for the ophthalmologist.
No full textThe eye has played a major role in human genomics including gene therapy. It is the fourth most common organ system after integument (skin, hair and nails), nervous system, and musculoskeletal system to be involved in genetic disorders. The eye is involved in single gene disorders and those caused by multifactorial etiology. Retinoblastoma was the first human cancer gene to be cloned. Leber hereditary optic neuropathy was the first mitochondrial disorder described. X-Linked red-green color deficiency was the first X-linked disorder described. The eye, unlike any other body organ, allows directly visualization of genetic phenomena such as skewed X-inactivation in the fundus of a female carrier of ocular albinism. Basic concepts of genetics and their application to clinical ophthalmological practice are important not only in making a precise diagnosis and appropriate referral, but also in management and genetic counseling
How genetics works? An illustrative case report
No full textIn this communication, we report the case of a four year old boy who presented with reduced vision in the right eye. He had visual acuity of light perception right eye and 6/12 in the left eye and anterior segment examination was normal. Fundus examination of the right eye showed a falciform retinal fold extending from the optic nerve temporally involving the entire retina with exudates within the falciform fold and dense pigmentation peripherally. The left eye showed mild macular temporal dragging of the vessels and 360° of peripheral laser scars. In addition he also had some characteristic systemic features such as developmental delay, obesity, dysmorphic facies and tapered fingers. Using this case as an example, we present a systematic, logical approach to a patient with a possible genetic disorder. The growing field of ocular genetics now allows for improved diagnosis using step-wise cost efficient testing as demonstrated herein
Novel <i>ABCA4</i> mutation leads to loss of a conserved C-terminal motif: implications for predicting pathogenicity based on genetic testing
No full textPurpose: Mutations in the ABCA4 gene result in a broad spectrum of severe retinal degeneration, including Stargardt macular dystrophy, fundus flavimaculatus, autosomal recessive retinitis pigmentosa, and cone-rod dystrophy. In addition to the detection of well-characterized mutations, genetic testing frequently yields novel variants of unknown significance. The purpose of this report is to describe an approach to aid in the assessment of genetic variants of unknown significance. Case report: We report an 11-year-old girl with Stargardt disease harboring novel compound heterozygous deletions of ABCA4 (c.850_857delATTCAAGA and c.6184_6187delGTCT). The pathogenicity of these variants was otherwise unknown. Both deletions introduce premature stop codons and are localized within the open reading frame of ABCA4. The c.850_857delATTCAAGA occurs early in the gene and leads to a significantly truncated protein of only 317 amino acids. The c.6184_6187delGTCT, is localized to the 3’ terminus of the ORF and results in removal of the last 161 out of 2,273 amino acids of ABCA4, including the VFVNFA motif, which has been shown to be critical in ABCA4 protein function. Homology-based protein modeling of ABCA4 harboring this deletion suggests significant alterations in the protein structure and function. Conclusions: Our analyses allowed us to classify novel variants in ABCA4 as being clearly loss-of-function mutations, and thus pathogenic variants. In cases of variants of unknown significance, appraising the protein structure-function consequences of genetic mutations using in silico tools may help to predict the clinical importance of variants of uncertain pathogenicity. </jats:sec
Genetics of the anterior segment dysgenesis
No full textThe anterior segment dysgeneses are a broad group of heterogeneous disorders characterized by developmental abnormalities of the anterior segment of the eye, including primary congenital aphakia, Peters sequence, aniridia, and Axenfeld–Rieger spectrum. These conditions can have overlapping phenotypes and both genotypic and phenotypic heterogeneity. This article provides a strategy for both phenotyping and then genotyping using a targeted stepwise approach
Mutations in <i>AGBL5</i> associated with Retinitis pigmentosa
No full textBackground: Retinitis pigmentosa (RP) is the leading cause of heritable retinal visual impairment. Clinically, it is characterized by a variable onset of progressive night blindness and visual field constriction. RP is characterized by wide genetic heterogeneity with a broad range of potential genes involved in the genesis of this disease. Very few cases have been reported of RP due to pathogenic variants in AGBL5.Materials and methods: We report two patients with RP and bilallelic pathogenic variants in AGBL5.Results: Genetic sequencing showed one homozygous AGBL5 missense variant in one patient and a homozygous nonsense variant in the other. These patients presented with progressive peripheral vision loss and nyctalopia. Their RP phenotypes were similar to previous reports in literature.Conclusion: These two cases provide further evidence regarding the relationship of pathogenic variants in AGBL5 as a cause of autosomal recessive RP
