ArticleHuman molecular genetics2014
Rare and common variants in extracellular matrix gene Fibrillin 2 (FBN2) are associated with macular degeneration.
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Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37citing papers in PubMed
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Who cites it
37 citing papers in PubMed, 62 citations in OpenAlex.
- Association of Rare Predicted Loss-of-Function Variants in Cellular Pathways with Sub-Phenotypes in Age-Related Macular Degeneration.Ophthalmology · 2018Trial
- An Integrated Proteomics and Genomics Approach to Identify Essential Protein Kinases During Human Trophoblast Development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Revisiting retinal and macular degeneration in the genomics era.Nature reviews. Genetics · 2026Review
- Differential regulation of myopia progression by ON and OFF stimulation in guinea pigs.Eye and vision (London, England) · 2026Article
- Case Report: A novel variant in fibrillin-2 identified in a congenital contractural arachnodactyly family with phenotypic heterogeneity.Frontiers in medicine · 2026Article
- ProteinMolecules (Basel, Switzerland) · 2025Review
- Genomic variations associated with risk and protection against vincristine-induced peripheral neuropathy in pediatric cancer patients.NPJ genomic medicine · 2024Article
- The Personalized Inherited Signature Predisposing to Non-Small-Cell Lung Cancer in Non-Smokers.Cancers · 2024Article
- Towards Uncovering the Role of Incomplete Penetrance in Maculopathies through Sequencing of 105 Disease-Associated Genes.Biomolecules · 2024Article
- Whole Genome Sequencing Identifies Novel Common and Low-Frequency Variants Associated With Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2023Article
- Proteomic profiling of retina and retinal pigment epithelium combined embryonic tissue to facilitate ocular disease gene discovery.Human genetics · 2023Article
- Intravitreal injection of fibrillin 2 (Fbn2) recombinant protein for therapy of retinopathy in a retina-specific Fbn2 knock-down mouse model.Scientific reports · 2023Article
- Proteomic profiling of retina and retinal pigment epithelium combined embryonic tissue to facilitate ocular disease gene discovery.Research square · 2023Article
- Case report: Identification of novelFrontiers in genetics · 2023Article
- Bioinformatic analysis identifies potential key genes in the pathogenesis of age-related macular degeneration.Indian journal of ophthalmology · 2022Article
- Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment.Human genetics · 2022Article
- Identification of NovelFrontiers in genetics · 2022Article
- Novel Epigenetic Clock Biomarkers of Age-Related Macular Degeneration.Frontiers in medicine · 2022Article
- Mutation analysis and prenatal diagnosis of a family with congenital contractural arachnodactyly.Molecular genetics & genomic medicine · 2021Article
- Autosomal Recessive Rod-Cone Dystrophy Associated With Compound Heterozygous Variants inFrontiers in cell and developmental biology · 2021Article
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Authors and funding
67 authors at 20 institutions in 7 countries.
Rinki RatnapriyaNeurobiology Neurodegeneration and Repair Laboratory.
Xiaowei ZhanCenter for Statistical Genetics, Department of Biostatistics and.
Robert N FarissBiological Imaging Core.
Kari E BranhamDepartment of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48109, USA.
David ZipprerNeurobiology Neurodegeneration and Repair Laboratory.
Christina F ChakarovaDepartment of Genetics, UCL-Institute of Ophthalmology, Bath Street, London EC1V 9EL, UK.
Yuri V SergeevOphthalmic Genetics and Visual Function Branch.
Maria M CamposBiological Imaging Core.
Mohammad OthmanDepartment of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48109, USA.
James S FriedmanNeurobiology Neurodegeneration and Repair Laboratory.
Arvydas MaminishkisSection of Epithelial and Retinal Physiology and Disease.
Naushin H WaseemDepartment of Genetics, UCL-Institute of Ophthalmology, Bath Street, London EC1V 9EL, UK.
Matthew BrooksNeurobiology Neurodegeneration and Repair Laboratory.
Harsha K RajasimhaNeurobiology Neurodegeneration and Repair Laboratory.
Albert O EdwardsInstitute for Molecular Biology, University of Oregon and Oregon Retina, Eugene, OR 97401, USA.
Andrew LoteryFaculty of Medicine, Clinical and Experimental Sciences, University of Southampton, Southampton SO16 6YD, UK.
Barbara E KleinDepartment of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and, Public Health, Madison, WI 53726, USA.
Barbara J TruittDepartment of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USA.
Bingshan LiCenter for Human Genetics Research, Vanderbilt University, Nashville, TN 37232, USA.
Debra A SchaumbergDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA, Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah, Salt Lake City, UT 84132, USA.
Denise J MorganDepartment of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah, Salt Lake City, UT 84132, USA.
Margaux A MorrisonDepartment of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah, Salt Lake City, UT 84132, USA.
Eric SouiedHôpital Intercommunal de Créteil, Hôpital Henri Mondor - Université Paris Est Créteil 94000, France.
Evangelia E TsironiDepartment of Ophthalmology, University of Thessaly School of Medicine, Larissa, Greece.
Felix GrassmannInstitute of Human Genetics, University of Regensburg, Regensburg 93053, Germany.
Gerald A FishmanDepartment of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
Giuliana SilvestriCentre for Vision and Vascular Science, Queen's University, Belfast, UK.
Hendrik P N SchollWilmer Eye Institute, Johns Hopkins University, 600 N. Wolfe Street, Baltimore, MD 21287, USA.
Ivana K KimRetina Service and Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
Jacqueline RamkeThe Fred Hollows Foundation, Auckland, New Zealand, School of Social Sciences, University of New South Wales, Sydney, Australia.
Jingsheng TuoSection of Immunopathology and.
Joanna E MerriamDepartment of Ophthalmology and.
John C MerriamDepartment of Ophthalmology and.
Kyu Hyung ParkDepartment of Ophthalmology, Seoul National University Bundang Hospital, Seoul 463-707, Republic of Korea.
Lana M OlsonCenter for Human Genetics Research, Vanderbilt University, Nashville, TN 37232, USA.
Lindsay A FarrerDepartments of Medicine (Section of Biomedical Genetics), Ophthalmology and Biostatistics, Neurology, Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA 02215, USA.
Matthew P JohnsonTexas Biomedical Research Institute, San Antonio, TX 78245, USA.
Neal S PeacheyCleveland Clinic Foundation, Cole Eye Institute, Cleveland, OH 44195, USA, Louis Stokes Cleveland VA Medical Center, Cleveland, OH 44195, USA.
Mark LathropDepartment of Genetics, Institut de la Vision - Inserm Université Pierre et Marie Curie UMR-S 968, Paris, France.
Robert V BaronDepartment of Human Genetics and.
Robert P IgoDepartment of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USA.
Ronald KleinDepartment of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and, Public Health, Madison, WI 53726, USA.
Stephanie A HagstromCleveland Clinic Foundation, Cole Eye Institute, Cleveland, OH 44195, USA.
Yoichiro KamataniDepartment of Genetics, Institut de la Vision - Inserm Université Pierre et Marie Curie UMR-S 968, Paris, France.
Tammy M MartinOregon Health & Science University, Portland, OR 97239, USA.
Yingda JiangDepartment of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Yvette ConleyHealth Promotion and Development, School of Nursing, 440 Victoria Building, 3500 Victoria St, Pittsburgh, PA 15261, USA.
Jose-Alan SahelDepartment of Genetics, Institut de la Vision - Inserm Université Pierre et Marie Curie UMR-S 968, Paris, France.
Donald J ZackWilmer Eye Institute, Johns Hopkins University, 600 N. Wolfe Street, Baltimore, MD 21287, USA.
Chi-Chao ChanSection of Immunopathology and.
Margaret A Pericak-VanceBascom Palmer Eye Institute and Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33125, USA.
Samuel G JacobsonDepartment of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Michael B GorinDepartment of Ophthalmology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Michael L KleinMacular Degeneration Center, Casey Eye Institute, Oregon Health and Science, University, Portland, OR 97201, USA.
Rando AllikmetsDepartment of Ophthalmology and Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Sudha K IyengarDepartment of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USA.
Bernhard H WeberInstitute of Human Genetics, University of Regensburg, Regensburg 93053, Germany.
Jonathan L HainesCenter for Human Genetics Research, Vanderbilt University, Nashville, TN 37232, USA.
Thierry LéveillardDepartment of Genetics, Institut de la Vision - Inserm Université Pierre et Marie Curie UMR-S 968, Paris, France.
Margaret M DeangelisDepartment of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah, Salt Lake City, UT 84132, USA.
Dwight StambolianDepartment of Ophthalmology, and Department of Genetics, University of Pennsylvania, Philadelphia, PA 9104, USA.
Daniel E WeeksDepartment of Human Genetics and Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Shomi S BhattacharyaDepartment of Genetics, UCL-Institute of Ophthalmology, Bath Street, London EC1V 9EL, UK.
Emily Y ChewClinical Trials Branch, Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
John R HeckenlivelyDepartment of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48109, USA.
Gonçalo R AbecasisCenter for Statistical Genetics, Department of Biostatistics and.
Anand SwaroopNeurobiology Neurodegeneration and Repair Laboratory, swaroopa@nei.nih.gov.
Inserm · FRCase Western Reserve University · USUniversity College London · GBUniversity of Michigan · USUniversity of Utah · USCancer Research And Biostatistics · USJohns Hopkins University · USOregon Health & Science University · USUniversity of Pittsburgh · USUniversity of Regensburg · DEVanderbilt University · USBoston University · USBrigham and Women's Hospital · USCenter for Human Genetics · USCleveland Clinic · USCleveland Eye Clinic · USColumbia University · USFred Hollows Foundation · AUHealth Promotion Services · USHôpital Intercommunal de Créteil · FR
Funding
Mechanisms, modeling and therapies of retinal and macular neurodegenerationZIAEY000546 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2015 to 2025
$36.3MProteins From Hereditary Eye Diseases: In-silico and Experimental StudiesZIAEY000476 · NEI · NATIONAL EYE INSTITUTE · PI SERGEEV, YURI · 2009 to 2025
$16.8MImaging Core UnitZICEY000459 · NEI · NATIONAL EYE INSTITUTE · PI FARISS, ROBERT · 2009 to 2025
$13.1MInstrumentation, Fabrication, and Design CoreP30EY019007 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Xin Zhang · 2010 to 2026
$12.9MHuman Retinal Pigment Epithelial PhysiologyZIAEY000419 · NEI · NATIONAL EYE INSTITUTE · PI SCHNEEWEIS, DAVID · 2009 to 2020
$12.0MGENETICS OF AGE-RELATED MACULOPATHYR01EY009859 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GORIN, MICHAEL B · 1993 to 2011
$11.5MGenetic Variation in Age-Related Macular DegenerationR01EY013435 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ALLIKMETS, RANDO L · 2001 to 2014
$7.7MGenetic susceptibility and common multi-factorial retinal/macular diseasesZIAEY000475 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2009 to 2014
$6.9MAge-Related Macular Degeneration: Genetic Variations and Animal ModelZIAEY000418 · NEI · NATIONAL EYE INSTITUTE · PI CHAN, CHI-CHAO · 2009 to 2015
$6.0MSIBLING STUDY OF AGE-RELATED MACULAR DEGENERATIONR01EY014458 · NEI · UNIVERSITY OF UTAH · PI DEANGELIS, MARGARET M · 2003 to 2010
$4.2MGenetic Epidemiology of Age-Related Macular DegenerationR01EY017362 · NEI · BRIGHAM AND WOMEN'S HOSPITAL · PI SCHAUMBERG, DEBRA A · 2007 to 2011
$2.9MA joint linkage/association strategy to interrogate AMD genetic susceptibilityR01EY021532 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI KLEIN, MICHAEL L · 2011 to 2014
$2.8MIntramural NIH HHS ZIA EY000418NEI NIH HHS EY013435NEI NIH HHS EY014458NEI NIH HHS EY016862NEI NIH HHS EY017362NEI NIH HHS EY019007NEI NIH HHS EY09859NEI NIH HHS P30 EY019007NEI NIH HHS R01 EY009859NEI NIH HHS R01 EY013435NEI NIH HHS R01 EY014458NEI NIH HHS R01 EY016862NEI NIH HHS R01 EY017362NEI NIH HHS R01 EY021532Wellcome Trust 076169/A
Abstract
Neurodegenerative diseases affecting the macula constitute a major cause of incurable vision loss and exhibit considerable clinical and genetic heterogeneity, from early-onset monogenic disease to multifactorial late-onset age-related macular degeneration (AMD). As part of our continued efforts to define genetic causes of macular degeneration, we performed whole exome sequencing in four individuals of a two-generation family with autosomal dominant maculopathy and identified a rare variant p.Glu1144Lys in Fibrillin 2 (FBN2), a glycoprotein of the elastin-rich extracellular matrix (ECM). Sanger sequencing validated the segregation of this variant in the complete pedigree, including two additional affected and one unaffected individual. Sequencing of 192 maculopathy patients revealed additional rare variants, predicted to disrupt FBN2 function. We then undertook additional studies to explore the relationship of FBN2 to macular disease. We show that FBN2 localizes to Bruch's membrane and its expression appears to be reduced in aging and AMD eyes, prompting us to examine its relationship with AMD. We detect suggestive association of a common FBN2 non-synonymous variant, rs154001 (p.Val965Ile) with AMD in 10 337 cases and 11 174 controls (OR = 1.10; P-value = 3.79 × 10(-5)). Thus, it appears that rare and common variants in a single gene--FBN2--can contribute to Mendelian and complex forms of macular degeneration. Our studies provide genetic evidence for a key role of elastin microfibers and Bruch's membrane in maintaining blood-retina homeostasis and establish the importance of studying orphan diseases for understanding more common clinical phenotypes.
Indexed as
Genetic Association StudiesGenetic VariationAdultAgedAmino Acid SequenceBruch MembraneDNA Mutational AnalysisExomeExtracellular MatrixFibrillin-2FibrillinsHigh-Throughput Nucleotide SequencingHumansMacular DegenerationMaleMeta-Analysis as TopicFBN2 protein, humanFibrillin-2FibrillinsMicrofilament Proteins
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