Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene

Nature
H C DietzS M Curristin

Abstract

Marfan syndrome is an inherited disorder of connective tissue manifested in the ocular, skeletal and cardiovascular systems. It is inherited as an autosomal dominant with high penetrance, but has great clinical variability. Linkage studies have mapped the Marfan locus to chromosome 15q15-21.3. There have been no reports of genetic heterogeneity in the syndrome. Following the identification of fibrillin (a glycoprotein component of the extracellular microfibril), immunohistopathological quantification of the protein in skin and fibroblast culture, and examination of fibrillin synthesis, extracellular transport, and incorporation into the extracellular matrix (D. M. Milewicz, R.E.P., E. S. Crawford and P. H. Byers, manuscript in preparation) have demonstrated abnormalities of fibrillin metabolism in most patients. A portion of the complementary DNA encoding fibrillin has been cloned and mapped by in situ hybridization to chromosome 15. Here we report that the fibrillin gene is linked to the Marfan phenotype (theta = 0.00; logarithm of the odds (lod) = 3.9) and describe a de novo missense mutation in the fibrillin gene in two patients with sporadic disease. We thus implicate fibrillin as the protein defective in patients with the ...Continue Reading

References

Aug 15, 1997·Microscopy Research and Technique·C M Kielty, C A Shuttleworth
Jul 22, 1998·Developmental Dynamics : an Official Publication of the American Association of Anatomists·B J RongishC D Little
Jan 1, 1993·Developmental Dynamics : an Official Publication of the American Association of Anatomists·B C GallagherC D Little
Aug 1, 1994·Developmental Dynamics : an Official Publication of the American Association of Anatomists·J M HurleM Solursh
Mar 31, 2012·American Journal of Medical Genetics. Part a·Jan J J AalbertsMaarten P van den Berg
Dec 29, 2004·The Anatomical Record. Part A, Discoveries in Molecular, Cellular, and Evolutionary Biology·Karine RobertNathalie Janel
Sep 1, 1993·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·F RamirezB Lee
Jan 1, 1995·Clinical Cardiology·T R McMinn, J Ross
Sep 25, 2002·Clinical Cardiology·Maria Cristinna PorcianiGian Franco Gensini
Mar 1, 1995·Journal of Clinical Pharmacology·S J PhelpsJ J Lima
Jan 1, 1992·Documenta Ophthalmologica. Advances in Ophthalmology·J P Ellant, S A Obstbaum
Jan 1, 1994·Mammalian Genome : Official Journal of the International Mammalian Genome Society·E T EverettJ S Norris
Nov 1, 1994·Mammalian Genome : Official Journal of the International Mammalian Genome Society·C GoldsteinL D Siracusa
Sep 29, 1995·Experientia·C D Little, B J Rongish
May 1, 1993·European Journal of Pediatrics·J ChristodoulouJ T Clarke
Sep 10, 2011·Herz·K KallenbachM Karck
Jul 10, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Wen-Jing WangXiao-Li Tian
Jan 13, 2010·International Urogynecology Journal·Symphorosa S C ChanKwong-Wai Choy
Aug 21, 2007·Calcified Tissue International·Tatjana Barisic-DujmovicStephen H Clark
Oct 2, 2009·Pediatric Cardiology·David KwiatkowskiRichard Meyer
Oct 2, 2007·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·E CheuretY Chaix
Jul 10, 2010·Human Genetics·Arun KumarSusan H Blanton
Jun 11, 2009·Cell and Tissue Research·Francesco Ramirez, L Y Sakai
Oct 25, 2006·Journal of Human Genetics·Takeshi Mizuguchi, Naomichi Matsumoto
Dec 2, 2011·Journal of Children's Orthopaedics·Beverlie L TingPaul D Sponseller
Mar 15, 2012·Current Atherosclerosis Reports·Guillaume Jondeau, Catherine Boileau
Aug 31, 2006·Current Treatment Options in Cardiovascular Medicine·Angela M Sharkey
Jan 24, 2002·Clinical Reviews in Allergy & Immunology·Mark L Johnson
Jan 26, 2008·Molecular Biotechnology·V Konstantinos KakavasNoulas V Argiris
Sep 9, 2011·Journal of Cardiovascular Translational Research·Daniel P JudgeRobert A Levine
Oct 1, 1992·Journal of Psychiatric Research·P F Pignatti, A E Turco
Nov 1, 1993·Journal of the American College of Cardiology·M J RomanR B Devereux

Citations

Apr 5, 1979·The New England Journal of Medicine·R E Pyeritz, V A McKusick
Jul 25, 1991·Nature·C L MaslenL Y Sakai
Apr 25, 1990·Nucleic Acids Research·J L Weber, P E May
Jul 19, 1990·The New England Journal of Medicine·D W HollisterR E Pyeritz
Aug 11, 1990·Nucleic Acids Research·J L Weber, P E May
Aug 11, 1990·Nucleic Acids Research·J L WeberP E May
Oct 4, 1990·The New England Journal of Medicine·K KainulainenL Peltonen
Nov 1, 1988·Genomics·Y NakamuraR White
Dec 1, 1986·The Journal of Cell Biology·L Y SakaiE Engvall
Oct 23, 1987·Cell·H Donis-KellerE S Lander

Related Concepts

Trichohepatoenteric Syndrome
Metabolic Process, Cellular
Thyroid Hormone Metabolism, Abnormal
Marfan Syndrome
Extracellular
Fibrillin
Glycoproteins
Cardiovascular System
Vision
Fibrillin Activity

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Sexual Dimorphism in Neurodegeneration

There exist sex differences in neurodevelopmental and neurodegenerative disorders. For instance, multiple sclerosis is more common in women, whereas Parkinson’s disease is more common in men. Here is the latest research on sexual dimorphism in neurodegeneration

HLA Genetic Variation

HLA genetic variation has been found to confer risk for a wide variety of diseases. Identifying these associations and understanding their molecular mechanisms is ongoing and holds promise for the development of therapeutics. Find the latest research on HLA genetic variation here.

Super-resolution Microscopy

Super-resolution microscopy is the term commonly given to fluorescence microscopy techniques with resolutions that are not limited by the diffraction of light. Here are the latest discoveries pertaining to super-resolution microscopy.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells.

Brain Lower Grade Glioma

Low grade gliomas in the brain form from oligodendrocytes and astrocytes and are the slowest-growing glioma in adults. Discover the latest research on these brain tumors here.

CD4/CD8 Signaling

Cluster of differentiation 4 and 8 (CD8 and CD8) are glycoproteins founds on the surface of immune cells. Here is the latest research on their role in cell signaling pathways.

Alignment-free Sequence Analysis Tools

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.