DOCSLIB.ORG

Optical Coherence Tomography Imaging of the Vitreoretinal Interface in Type II Stickler Syndrome

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Optical Coherence Tomography Imaging of the Vitreoretinal Interface in Type II Stickler Syndrome Optical Coherence Tomography Imaging of the Vitreoretinal Interface in Type II Stickler Syndrome Abstract Stickler syndrome was previously characterized post-enucleation by incarcerated vitreous collagen within glial tissue of patients with retinal detachments.1 This study demonstrates similar vitreoretinal interfaces in vivo using OCT imaging of three siblings with Stickler Syndrome. I. Case History Patient A: 1. Demographics: 38 YOWM 2. Chief Complaint: None 3. Ocular, medical history: Type II Stickler Syndrome, diagnosed age 7 4. Medications: None 5. Other salient information: Mild myopia 6. Family History a. Six Retinal detachments and two flap tears among first-degree relatives b. Twelve Retinal detachments among second-degree relatives c. Fourteen Retinal detachments among third-degree relatives Patient B: 1. Demographics: 36 YOWM 2. Chief Complaint: None 3. Ocular, medical history: a. Type II Stickler Syndrome, diagnosed age 5 b. Flap tear OD, age 17, treated with retinopexy c. Flap tear OS, age 20, treated with retinopexy d. Vitreal tuft with photopsias OD, age 22, treated with retinopexy e. Central Serous Retinopathy OD, age 23, resolved 4. Medications: None 5. Other salient information: Mild myopia 6. Family History a. Six Retinal detachments among first-degree relatives b. Twelve Retinal detachments among second-degree relatives c. Fourteen Retinal detachments among third-degree relatives Patient C: 1. Demographics: 34 YOWF 2. Chief Complaint: None 3. Ocular, medical history: a. Type II Stickler Syndrome, diagnosed age 3 b. Congenital cataracts OU 4. Medications: None 5. Other salient information: Mild myopia and moderate astigmatism 6. Family History a. Six Retinal detachments and two flap tears among first-degree relatives b. Twelve Retinal detachments among second-degree relatives c. Fourteen Retinal detachments among third-degree relatives II. Pertinent Findings Patient A: 1. Clinical: a. BCVA: 20/15 OD, OS b. Anterior segment: unremarkable c. TA: 18 OD, OS d. Posterior segment: Significant vitreal syneresis in excess to age-appropriate findings and vitreous beading e. OCT: Abnormal vitreal architecture; significant tubular collagen condensations at the vitreoretinal interface with approximation to the ILM, non-homogenous posterior hyaloid face OU 2. Physical: No systemic manifestations of Stickler Syndrome 3. Laboratory studies: None 4. Radiology studies: None Patient B: 1. Clinical: a. BCVA: 20/20 OD, OS b. Anterior segment: unremarkable c. TA: 16 OD, OS d. Posterior segment: i. Significant vitreal syneresis in excess to age-appropriate findings and vitreous beading ii. Flap tear superior temporal OD, superior nasal OS, adequate barricade laser iii. Faint laser scars temporal OD iv. RPE disruption inferior nasal to fovea OD v. Lattice superior OD e. OCT: Abnormal vitreal architecture; significant tubular collagen condensations at the vitreoretinal interface with approximation to the ILM, non-homogenous posterior hyaloid face OD>OS 2. Physical: No systemic manifestations of Stickler Syndrome 3. Laboratory studies: None 4. Radiology studies: None Patient C: 1. Clinical: a. BCVA: 20/20 OD, 20/25- OS b. Anterior segment: Lens: Scattered punctate opacities in cortex OU, dense congenital cataract superior temporal OS c. TA: 19 OD, 16 OS d. Posterior segment: i. Significant vitreal sheathing and vitreous beading ii. Lattice without holes superior and superior nasal OD, superior and inferior temporal OS e. OCT: Unremarkable OD, OS? 2. Physical: No systemic manifestations of Stickler Syndrome 3. Laboratory studies: None 4. Radiology studies: None III. Differential Diagnosis 1. Differentials for Type II Stickler Syndrome:5 6 a. Type I, III, and IV Stickler Syndrome b. Knobloch Syndrome c. Wagner Syndrome d. Multiple Epiphyseal Dysplasia e. Metatropic Dysplasia f. Erosive Vitreoretinopathy g. Marshall Syndrome h. Weissenbacker-Zweymuller Syndrome/OSMED i. Marfan Syndrome j. Spondyloepiphyseal Dysplasia Congenita k. Kniest Dysplasia 2. Differentials for vitreal beading: None found in literature IV. Diagnosis and Discussion Stickler syndrome is arguably the most common autosomal dominant chondrodysplasia, characterized by ophthalmic abonormalities, early joint hypermobility and late osteoarthritis, sensorineural deafness, and variable orofacial features, including depressed nasal bridge, midline clefting, and micrognathia.6 Ophthalmic manifestations include paravascular lattice degeneration, mild to moderate myopia, congenital cataracts, retinal tears and detachments, and pathognomonic abnormalities in vitreous architecture.2 6 Type I Stickler syndrome, compromising 75% of all Stickler patients, occurs with mutations in the COL2AI gene causing a variation in type II collagen leading to a “membranous” anomaly of the vitreous cavity, while patients with type II Sticklers develop mutations in COLIIAI, leading to type XI collagen abnormalities and a “beaded” vitreous phenotype.2 One study by ME MacRae et al., utilizing histological and electron microscopic examination of an enucleated globe of a patient with type I Stickler syndrome, discovered paramount abnormalities within the vitreoretinal interface, specifically adherence between vitreous collagen and retinal glial tissue in areas of detachment, in some cases forming a retrolental membrane of incarcerated collagen within glial strands.1 There are currently no studies in the literature that assess the presence or absence of collagen abnormalities within the posterior vitreous and vitreoretinal interface using OCT imaging of patients with type II Stickler syndrome. V. Treatment, Management Treatment for Stickler Syndrome is palliative, usually involving hearing assessment and management of sensorineural deafness, as well as thorough, lifelong ophthalmic care including corrective lenses for refractive error, cataract surgery, prophylactic retinopexy for retinal tears, and retinal detachment repair when indicated. Because Stickler Syndrome is the leading cause of rhegmatogenous retinal detachments in youth, patient education about symptoms of retinal detachment is crucial upon diagnosis.6 VI. Conclusion This study demonstrates the ability of OCT imaging to elucidate abnormal vitreous architecture in Type II Stickler Syndrome. This method has not been previously explored in the literature. While statistically underpowered, there does not appear to be strong correlation between OCT findings and the prevalence of retinal defects. Bibliography 1. Macrae, M. E., Patel, D. V., Richards, A. J. et al. (2005, December 2). Type 1 Stickler syndrome: A histological and ultrastructural study of an untreated globe. Eye, 20(9), 1061-1067. doi:10.1038/sj.eye.6702129. 2. Poulson, A. V., Hooymans, J M M., Richards A. J. et al. (2004). Clinical features of type 2 Stickler syndrome. Journal of Medical Genetics, 41(8). doi:10.1136/jmg.2004.018382. 3. Richards, A. J., Mcninch, A., Martin, H. et al. (2010). Stickler syndrome and the vitreous phenotype: Mutations in COL2A1 and COL11A1. Human Mutation Hum. Mutat., 31(6). doi:10.1002/humu.21257. 4. Rose, P. S., Levy, H. P., Liberfarb, R. M. et al. (2005). Stickler syndrome: Clinical characteristics and diagnostic criteria. Am. J. Med. Genet. American Journal of Medical Genetics Part A, 138A(3), 199-207. doi:10.1002/ajmg.a.30955. 5. Sebag, J. (2014). Vitreous: In health and disease. Springer Science+Business Media. doi:10.1007/978-1-4939-1086-1. 6. Snead, M. P., & Yates, J. R. (1999). Clinical and molecular genetics of Stickler syndrome. Journal of Medical Genetics, 36, 353-359. doi:10.1136/jmg.36.5.353. 7. Wang, X., Xiaoyun, J., Xueshan, X. et al. (2016, June 23). Mutation survey and genotype- phenotype analysis of COL2A1 and COL11A1 genes in 16 Chinese patients with Stickler syndrome. Molecular Vision, 22, 697-704. .
Load more

Recommended publications
  • Whole Exome Sequencing Gene Package Vision Disorders, Version 6.1, 31-1-2020
    Whole Exome Sequencing Gene package Vision disorders, version 6.1, 31-1-2020 Technical information DNA was enriched using Agilent SureSelect DNA + SureSelect OneSeq 300kb CNV Backbone + Human All Exon V7 capture and paired-end sequenced on the Illumina platform (outsourced). The aim is to obtain 10 Giga base pairs per exome with a mapped fraction of 0.99. The average coverage of the exome is ~50x. Duplicate and non-unique reads are excluded. Data are demultiplexed with bcl2fastq Conversion Software from Illumina. Reads are mapped to the genome using the BWA-MEM algorithm (reference: http://bio-bwa.sourceforge.net/). Variant detection is performed by the Genome Analysis Toolkit HaplotypeCaller (reference: http://www.broadinstitute.org/gatk/). The detected variants are filtered and annotated with Cartagenia software and classified with Alamut Visual. It is not excluded that pathogenic mutations are being missed using this technology. At this moment, there is not enough information about the sensitivity of this technique with respect to the detection of deletions and duplications of more than 5 nucleotides and of somatic mosaic mutations (all types of sequence changes). HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered % covered gene symbol gene ID >10x >20x >30x ABCA4 Cone-rod dystrophy 3, 604116 601691 94 100 100 97 Fundus flavimaculatus, 248200 {Macular degeneration, age-related, 2}, 153800 Retinal dystrophy, early-onset severe, 248200 Retinitis pigmentosa 19, 601718 Stargardt disease
    [Show full text]
  • Ophthalmology
    Ophthalmology Information for health professionals MEDICAL GENETIC TESTING FOR OPHTHALMOLOGY Recent technologies, in particularly Next Generation Sequencing (NGS), allows fast, accurate and valuable diagnostic tests. For Ophthalmology, CGC Genetics has an extensive list of medical genetic tests with clinical integration of results by our Medical Geneticists. 1. EXOME SEQUENCING: Exome Sequencing is a very efficient strategy to study most exons of a patient’s genome, unraveling mutations associated with specific disorders or phenotypes. With this diagnostic strategy, patients can be studied with a significantly reduced turnaround time and cost. CGC Genetics has available 2 options for Exome Sequencing: • Whole Exome Sequencing (WES), which analyzes the entire exome (about 20 000 genes); • Disease Exome by CGC Genetics, which analyzes about 6 000 clinically-relevant genes. Any of these can be performed in the index case or in a Trio. 2. NGS PANELS For NGS panels, several genes associated with the same phenotype are simultaneously sequenced. These panels provide increased diagnostic capability with a significantly reduced turnaround time and cost. CGC Genetics has several NGS panels for Ophthalmology that are constantly updated (www.cgcgenetics.com). Any gene studied in exome or NGS panel can also be individually sequenced and analyzed for deletion/duplication events. 3. EXPERTISE IN MEDICAL GENETICS CGC Genetics has Medical Geneticists specialized in genetic counseling for ophthalmological diseases who may advice in choosing the most appropriate
    [Show full text]
  • Basement Membranes in Diseases Affecting the Eye, Kidney
    Van Agtmael, T. and Bruckner-Tuderman, L. (2010) Basement membranes and human disease. Cell and Tissue Research, 339 (1). pp. 167-188. ISSN 0302-766X http://eprints.gla.ac.uk/35275/ Deposited on: 30 August 2010 Enlighten – Research publications by members of the University of Glasgow http://eprints.gla.ac.uk Basement membranes and human disease Tom van Agtmael§ and Leena Bruckner-Tuderman* § Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, U.K. and * Dept. of Dermatology, University Medical Center Freiburg and Freiburg Institute for Advanced Studies, Freiburg, Germany Corresponding authors: Tom Van Agtmael Faculty of Biomedical and Life Sciences, Davidson Building, University of Glasgow, University Avenue, Glasgow UK, [email protected],. Leena Bruckner-Tuderman Department of Dermatology, University Medical Center Freiburg, Hauptstr. 7, 79104 Freiburg, Germany. E-mail: [email protected] Keywords: basement membrane, laminin, collagen, laminin, nidogen Abbreviations BM: basement membrane, NMJ neuromuscular junction, DEJ dermo epidermal junction, SJS Schwartz Jampel syndrome, DDSH Dyssegmental dysplasia silverman handmaker type, EB epidermolysis bullosa, GBM glomerular basement membrane 1 Abstract In 1990 the role of basement membranes in human disease was established by the identification of COL4A5 mutations in Alport’s syndrome. Since then the number of diseases caused by mutations in basement membrane components has steadily increased as has our understanding of the roles of basement membranes in organ development and function. However, many questions remain as to the molecular and cellular consequences of these mutations and how they lead to the observed disease phenotypes. Despite this, exciting progress has recently been made with potential treatment options for some of these so far incurable diseases.
    [Show full text]
  • A Review of Hypermobility Syndromes and Chronic Or Recurrent Musculoskeletal Pain in Children Marco Cattalini1, Raju Khubchandani2 and Rolando Cimaz3*
    Cattalini et al. Pediatric Rheumatology (2015) 13:40 DOI 10.1186/s12969-015-0039-3 REVIEW Open Access When flexibility is not necessarily a virtue: a review of hypermobility syndromes and chronic or recurrent musculoskeletal pain in children Marco Cattalini1, Raju Khubchandani2 and Rolando Cimaz3* Abstract Chronic or recurrent musculoskeletal pain is a common complaint in children. Among the most common causes for this problem are different conditions associated with hypermobility. Pediatricians and allied professionals should be well aware of the characteristics of the different syndromes associated with hypermobility and facilitate early recognition and appropriate management. In this review we provide information on Benign Joint Hypermobility Syndrome, Ehlers-Danlos Syndrome, Marfan Syndrome, Loeys-Dietz syndrome and Stickler syndrome, and discuss their characteristics and clinical management. Keywords: Hyperlaxity, Musculoskeletal pain, Ehlers-Danlos, Marfan, Loeys-Dietz, Stickler Introduction Review Chronic or recurrent musculoskeletal pain is a common Benign joint hypermobility syndrome (BJHS) complaint in children, affecting between 10 % and 20 % Children with hypermobile joints by definition display a of children. It is one of the more frequent reasons for range of movement that is considered excessive, taking seeking a primary care physician’sevaluationandpos- into consideration the age, gender and ethnic background sible rheumatology referral [1, 2]. A wide variety of of the individual. It is estimated that at least 10–15 % of non-inflammatory conditions may cause musculoskel- normal children have hypermobile joints and the term etal pain in the pediatric age, and the most common joint hypermobility syndrome (JHS) is reserved to the causes seen by paediatric rheumatologists include cases of joint hypermobility associated with symptoms conditions associated with hypermobility.
    [Show full text]
  • Inherited Connective Tissue Disorders of Collagens: Lessons from Targeted Mutagenesis
    13 Inherited Connective Tissue Disorders of Collagens: Lessons from Targeted Mutagenesis Christelle Bonod-Bidaud and Florence Ruggiero Institut de Génomique Fonctionnelle de Lyon, ENS de Lyon, UMR CNRS 5242, University Lyon 1, France 1. Introduction The extracellular matrix (ECM) is the cell structural environment in tissues and organs. The ECM is a dynamic structure that it is constantly remodelled. It contributes to tissue integrity and mechanical properties. It is also essential for maintaining tissue homeostasis, morphogenesis and differentiation, which it does, through specific interactions with cells. The ECM is composed of a mixture of water and macromolecules classified into four main categories: collagens, proteoglycans, elastic proteins, and non-collagenous glycoproteins (also called adhesive glycoproteins). The nature, concentration and ratio of the different ECM components are all important factors in the regulation of the assembly of complex tissue-specific networks tuned to meet mechanical and biological requirements of tissues. Collagens form a superfamily of 28 trimeric proteins, distinguishable from the other ECM components by their particular abundance in tissues (collagens represent up to 80-90% of total proteins in skin, tendon and bones) and their capacity to self-assemble into supramolecular organized structures (the best known being the banded fibers). The collagen superfamily is highly complex and shows a remarkable diversity in structure, tissue distribution and function (Ricard-Blum and Ruggiero, 2005). The importance
    [Show full text]
  • Blueprint Genetics Vitreoretinopathy Panel
    Vitreoretinopathy Panel Test code: OP0701 Is a 24 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion / diagnosis of vitreoretinopathy. The genes on this panel are included in the Retinal Dystropy Panel. About Vitreoretinopathy Vitreoretinal diseases are characterised by the degeneration of the vitreous and retina of the eye. Several types of vitreoretinopathies exist giving rise to a spectrum of phenotypic presentations such as retinal detachment, optically empty vitreous, fibrillary condensation, cataract, and neovascularization. The condition includes familial exudative vitreoretinopathy, snowflake vitreoretinal degeneration, Norrie disease, Wagner syndrome, Stickler syndrome and Knobloch syndrome. The vitreoretinopathies may be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. For instance, autosomal dominant familial exudative vitreoretinopathy (FEVR) is caused by mutations in FZD4; LRP5 has been associated with both autosomal dominant and recessive cases and NDP with X-linked FEVR. The clinical presentation and the disease course can be highly variable. The prevalence of FEVR is unknown, but it is a rare disorder. Availability 4 weeks Gene Set Description Genes in the Vitreoretinopathy Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ATOH7 Persistent hyperplastic primary vitreous, autosomal recessive AR 4 9 BEST1 Vitreoretinochoroidopathy, Microcornea, Rod-cone dystrophy, Posterior AD/AR 62 318 staphyloma, Bestrophinopathy,
    [Show full text]
  • Knobloch Syndrome Associated with Polymicrogyria and Early Onset of Retinal Detachment: Two Case Reports Robert J
    White et al. BMC Ophthalmology (2017) 17:214 DOI 10.1186/s12886-017-0615-z CASE REPORT Open Access Knobloch syndrome associated with Polymicrogyria and early onset of retinal detachment: two case reports Robert J. White, Yao Wang, Peter Tang and Sandra R. Montezuma* Abstract Background: Knobloch Syndrome (KS) is a rare congenital syndrome characterized by occipital skull defects and vitreoretinal degeneration. Retinal detachment (RD) often occurs at the end of the first decade of life or later. Aside from occipital skull defects, central nervous system abnormalities are uncommon. Case presentations: We report on two siblings with KS. The first, a seven month old male, presented with nystagmus and was found to have a serous RD and a tessellated retinal appearance. His sister had a history of multiple visual abnormalities and had a similar retinal appearance although no signs of RD, but retina staphylomas. Genetic testing performed on both siblings showed a mutation in COL18A1, diagnostic of KS. MRI of both siblings demonstrated polymicrogyria but did not show occipital defects. Conclusions: Although several families with KS have been described previously, our case is noteworthy for several reasons. The RD observed in our first patient occurred at an early age, and we find evidence of only one patient with KS who had an RD identified at an earlier age. The findings of polymicrogyria are not characteristic of KS, and we found only a few previous reports of this association. Additionally, we review potential treatment options for this condition. Keywords: Knobloch syndrome, COL18A1, Retinal detachment, Polymicrogyria, Case report Background including pachygyria, polymicrogyria and cerebellar Knobloch Syndrome (KS) is a rare autosomal recessive atrophy among other findings [2].
    [Show full text]
  • One Vision2012
    Illinois Eye and Ear Infirmary UIC Department of Ophthalmology & Visual Sciences ONE VISION2012 IN THIS ISSUE A MEssaGE FRom THE DEAN 2 News "I am pleased to welcome Rohit Varma, MD, MPH, as Chair 8 Innovations of the Illinois Eye and Ear Infirmary, University of Illinois at 12 Patient Profile Chicago Department of Ophthalmology & Visual Sciences 14 Giving and Associate Dean for Strategic Planning at the UIC 20 Endowment Activity College of Medicine. Dr. Varma is a highly accomplished physician-scientist and translational investigator who studies 22 Faculty the development of eye diseases in minority populations 25 Publications and examines novel biological, genetic and lifestyle factors 34 Sponsored Research related to the risk of developing eye diseases. He is an expert 36 Clinical Investigations and Trials on changes in the optic nerve in glaucoma and on new 38 Residents and Fellows imaging techniques in the early diagnosis of glaucomatous 41 Alumni optic nerve damage. Under his leadership, the Department of Ophthalmology & Visual Sciences begins a new era of clinical and research excellence." Dimitri T. Azar, MD, MBA | Dean, College of Medicine Dean Dimitri Azar (left) and Dr. Rohit Varma CREDITS Managing Editor Julie Daraska Editors Carol Chaplin & Margaret Doyle Designers Studio Deluxe & Lisa Birmingham Contributors Margaret Chervinko, Laurie Walker Candace Pearson & Margaret Doyle Photography Cathy Carroll, Joshua Clark, Roberta Dupuis-Devlin, Mark Janowicz & Walter Urie One Vision 2012 1 A MEssaGE FRom THE DEPARTMENT CHaiR "I am deeply honored by the trust that Dean Azar has placed in me to lead the Illinois Eye and Ear Infirmary, UIC Department of Ophthalmology & Visual Sciences to a new era of educational, clinical and research excellence.
    [Show full text]
  • Test Requisition Form (Dna & Genetic Tests)
    TEST REQUISITION FORM (DNA & GENETIC TESTS) INCLUDE THE FIRST 3 PAGES OF THIS FORM WITH SPECIMEN. Before sending specimens, please contact us for pre-authorization procedures. Samples received without billing pre-authorization cannot be processed. REPORTING INFORMATION ADDITIONAL REPORTS Ordering Physician or Genetic Counselor Copy of report should be sent to Name: Name: Email: Email: Institution: Fax: ( ) Address: City, State, Zip: Name: Phone: ( ) Email: Fax: ( ) Fax: ( ) PATIENT INFORMATION Patient's Last Name, First Name, MI Birthdate (mm/dd/yyyy) Gender M F Indication or reason for testing (check all that apply) Diagnosis Asymptomatic family member Confirm recorded mutation: High risk population (state Ancestry or Ethnic background below) Prenatal screening Ongoing pregnancy Other: Ancestry or Ethnic Background (check all that apply) Patient's country of origin Ethnic Background Hispanic Jewish Asian Middle-East Americas Europe Africa Australia Hospital or Clinic Patient ID Specimen ID Diagnosis (ICD9 codes) SPECIMEN INFORMATION (REQUIRED) Specimen Date/Time Collected Collected by (initial) Specimen Type (If other, please contact us before shipping) / / _____:_____ AM/PM Buccal Blood Other: Specimen may be submitted as whole blood or buccal epithelial cells (2 swabs / patient). Transport at room temperature. For other specimens and more details, see page labeled "Specimen Requirements". TESTS REQUESTED (Ask us to customize the requisition form for your practice) Test No. Test Name 1. Stat 2. Stat 3. Stat Test Names are found on the list at the end of this form. The tests will be performed in the order listed. Turnaround times are usually less than 5 weeks following receipt of specimen. Sequential panels of several large genes will take longer depending on which gene positive results are found.
    [Show full text]
  • Collagen VI), Multiplexin (E.G
    Essays in Biochemistry (2019) 63 297–312 https://doi.org/10.1042/EBC20180071 Review Article Basement membrane collagens and disease mechanisms Anna Gatseva1, Yuan Yan Sin1, Gaia Brezzo1,2 and Tom Van Agtmael1 1Institute of Cardiovascular and Medical Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, United Kingdom; 2Centre for Discovery Brain Sciences, Medical Downloaded from https://portlandpress.com/essaysbiochem/article-pdf/63/3/297/844117/ebc-2018-0071c.pdf by University of Glasgow user on 14 October 2019 School, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom Correspondence: Tom Van Agtmael ([email protected]) Basement membranes (BMs) are specialised extracellular matrix (ECM) structures and col- lagens are a key component required for BM function. While collagen IV is the major BM collagen, collagens VI, VII, XV, XVII and XVIII are also present. Mutations in these collagens cause rare multi-systemic diseases but these collagens have also been associated with major common diseases including stroke. Developing treatments for these conditions will require a collective effort to increase our fundamental understanding of the biology of these collagens and the mechanisms by which mutations therein cause disease. Novel insights into pathomolecular disease mechanisms and cellular responses to these mutations has been exploited to develop proof-of-concept treatment strategies in animal models. Com- bined, these studies have also highlighted the complexity of the disease mechanisms and the need to obtain a more complete understanding of these mechanisms. The identification of pathomolecular mechanisms of collagen mutations shared between different disorders represent an attractive prospect for treatments that may be effective across phenotypically distinct disorders.
    [Show full text]
  • Three Cases of Molecularly Confirmed Knobloch Syndrome
    Ophthalmic Genetics ISSN: 1381-6810 (Print) 1744-5094 (Online) Journal homepage: https://www.tandfonline.com/loi/iopg20 Three cases of molecularly confirmed Knobloch syndrome Irina Balikova, Nuri Serdal Sanak, Depasse Fanny, Guillaume Smits, Julie Soblet, Elfride de Baere & Monique Cordonnier To cite this article: Irina Balikova, Nuri Serdal Sanak, Depasse Fanny, Guillaume Smits, Julie Soblet, Elfride de Baere & Monique Cordonnier (2020) Three cases of molecularly confirmed Knobloch syndrome, Ophthalmic Genetics, 41:1, 83-87, DOI: 10.1080/13816810.2020.1737948 To link to this article: https://doi.org/10.1080/13816810.2020.1737948 © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. Published online: 17 Mar 2020. Submit your article to this journal Article views: 269 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=iopg20 OPHTHALMIC GENETICS 2020, VOL. 41, NO. 1, 83–87 https://doi.org/10.1080/13816810.2020.1737948 CASE REPORT Three cases of molecularly confirmed Knobloch syndrome Irina Balikovaa,b, Nuri Serdal Sanakc, Depasse Fannyd, Guillaume Smitse, Julie Soblete, Elfride de Baeref, and Monique Cordonnierc aDepartment of Ophthalmology, University Hospital Leuven, Leuven, Belgium; bDepartment of Ophthalmology, Children Hospital Queen Fabiola, Brussels, Belgium; cDepartment of Ophthalmology, University Hospital Erasme, Brussels, Belgium; dOphthalmology Service, University Hospital Charleroi, Charleroi, Belgium; eDepartment of Genetics, University Hospital Erasme, Brussels, Belgium; fCenter for Medical Genetics, University Hospital Ghent, Ghent, Belgium ABSTRACT ARTICLE HISTORY Background: Knobloch syndrome (OMIM 267750) is a rare autosomal recessive disorder due to genetic Received October 21, 2019 defects in the COL18A1 gene.
    [Show full text]
  • Common Variants in the COL2A1 Gene Are Associated with Lattice Degeneration of the Retina in a Japanese Population
    Molecular Vision 2019; 25:843-850 <http://www.molvis.org/molvis/v25/843> © 2019 Molecular Vision Received 25 April 2019 | Accepted 3 December 2019 | Published 5 December 2019 Common variants in the COL2A1 gene are associated with lattice degeneration of the retina in a Japanese population Shinya Okazaki,1 Akira Meguro,1 Ryuichi Ideta,2 Masaki Takeuchi,1 Junichi Yonemoto,1 Takeshi Teshigawara,1,3,4 Takahiro Yamane,1 Eiichi Okada,5 Hidenao Ideta,2 Nobuhisa Mizuki1 1Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan; 2Ideta Eye Hospital, Kumamoto, Kumamoto, Japan; 3Yokosuka Chuoh Eye Clinic, Yokosuka, Kanagawa, Japan; 4Tsurumi Chuoh Eye Clinic, Yokohama, Kanagawa, Japan; 5Okada Eye Clinic, Yokohama, Kanagawa, Japan Purpose: Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion that predisposes the patient to retinal detachment. It has been suggested that collagen type II alpha 1 (COL2A1) gene vari- ants may contribute to the development of disorders associated with retinal detachment. Here we investigated whether COL2A1 gene variants were associated with the risk of lattice degeneration of the retina. Methods: We recruited 634 Japanese patients with lattice degeneration of the retina and 1694 Japanese healthy controls. We genotyped 13 tagging single-nucleotide polymorphisms (SNPs) in COL2A1. We also performed imputation analysis to evaluate the potential association of un-genotyped COL2A1 SNPs, involving the imputation of 65 SNPs. Results: Two intronic SNPs—rs1793954 and rs1635533—were significantly associated with lattice degeneration of the retina. The SNP rs1793954 showed the strongest association, with its C allele carrying an increased disease risk (p = 0.0016, corrected p = 0.021, OR = 1.25).
    [Show full text]