Molecular and Cellular Mechanisms

Ana Margarida Guilherme Carla Hovenkamp

Joana Goucha Sofia Néri

Biologia Celular e Molecular - 2012/2013

The Extracellular Matrix

http://dc442.4shared.com/doc/rckV-mEb/preview.html

Outline of the primary structure of fibrillin 1. Note the multiple calcium-binding sites and the interactive sites with other extracellular matrix components.

http://www.alaccsa.com/tc_cat.htm0

Chromosome no. 15 which states the mutation that causes Marfan Syndrome

http://bioinfo-btg10-grupo04.wikispaces.com/1.+Introducci%C3%B3n

FBN1 gene with multiple domains

http://bioinfo-btg10-grupo04.wikispaces.com/1.+Introducci%C3%B3n

http://be115.blogspot.pt/2010/11/bone-matrix-to-growth-factors-location.html

Distinct contributions of osteoblast-produced fibrillin-1 and fibrillin-2 microfibrils to osteogenic differentiation through the differential regulation of endogenous TGF-β and BMP signals that together calibrate the rate of bone formation

http://www.historiadelamedicina.org/Marfan.html

Described by Dr. Antoine Marfan in 1896;

Affects both men and women of any race or ethnic origin;

Connective tissue “connects”, provides structural support and determines the elasticity of the body's organs, bones and ligaments.

http://unecfarmacia.blogspot.pt/2011/04/sindrome-de-marfan-progeria-e-parkinson.html

The connective tissue in the heart, lungs, eyes and mostly skeletal and nervous systems can stretch and weaken, due to the malfunctioning of the fibrilin protein;

This syndrome can be of autosomal dominant inheritance or it may appear for the first time in a family in a child of unaffected parents (25 to 30% of the cases).

Skeleton • Tall;

• Slim;

• Long, thin limbs;

• Long fingers and toes;

• Abnormal joint flexibility.

• Small lower jaw;

• High, arched palate;

• Deep-set eyes;

• Flat feet;

• Pectus excavatum (sternum indentation);

• Pectus carinatum (sternum protusion);

• Crowded teeth;

• Scoliosis. http://www.nasagap.com/marfan-syndrome-symptoms-cause-effects-treatment-and-cure/

http://www.childrenshospital.org/az/Site543/mainpageS543P0.html

Eyes

• Lens dislocation;

• Myopia;

• Glaucoma;

• Cataracts;

• Retinal detachment.

Cardiovascular system

• Aortic aneurysm;

• Heart valve problems ;

• Aortic dissection.

Stretch marks

• Shoulders;

• Hips;

• Lower back.

http://www.genetest.pt/index.php?id=4&testid=9

http://www.gfmer.ch/genetic_diseases_v2/gendis_detail_list.php?cat3=1258

http://www.njcponline.com/articles/2012/15/3/images/NigerJClinPract_2012_15_3_364_100653_f4.jpg

• Physical examination

• Medical and family history

• Ghent criteria

• Genetic testing

Gene

FBN1 at 15q21.1

TGFβR1 at 9q33-34

TGFβR2 at 3p22

Clinical Sensitivity

Up to 90% of patients with a clinical diagnosis of MFS have a FBN1 mutation.

Those who are FBN1 negative may have a TGFβR2 mutation (up to 21%) or aTGFβR1 mutation (up to 4%).

• Prenatal testing

Chorionic villus sampling (CVS)

Amniocentesis

http://www.tumblr.com/tagged/marfan%20syndrome

• Treatment will help improve the quality of life and lengthen lifespan;

• Monitoring by doctors is onde of the most important steps.

http://cdn.controlinveste.pt/Storage/ng1101715.jpg (4/03, 21h18)

Nevertheless, these patients must have some special cares regarding:

Hearth problems;

Eyesight;

Orthopedics;

Lung problems.

(1) http://ennioss.files.wordpress.com/2012/01/sistema-cardiovascular-19.jpg (2) http://www.cintramedica.pt/admin/imagens_noticias/thumb.php?img=4&maximox=&maximoy= (3) http://www.tatame.com.br/media/Beneficios-do-treino-especifico-para-a-coluna_1.jpg

In 2007, at Johns Hopkins, a clinical trial was started to study the uses of losartan to decrease the formation of aortic aneurysms.

http://www.gghjournal.com/volume22/3/ab08.cfm (04/03, 21h47)

• DEAN, John CS. “Marfan syndrome: clincial diagnosis and management” in European Journal of Human Genetics, 2007;

• ALBERTS, B. et al. Molecular Biology of the Cell. ARTMED Editora, 2006. Pages 1102 and 1103;

• http://ambrygen.com/tests/marfan-aneurysm-and-related-disorders-next-gen-sequencing-panel (04/03/2013 - 12h25);

• http://en.wikipedia.org/wiki/Marfan_syndrome#Management (04/03/2013 - 9h55);

• http://pcpgm.partners.org/lmm/tests/connective-tissue/marfan (04/03/2013 - 10h10);

• http://www.eurordis.org/pt-pt/content/sindrome-de-marfan-doenca-silenciosa (03/03/2013 – 17h15);

• http://www.marfan.ca/content/view/58/1/ (02/03/2013 – 19h15);

• http://www.marfan.ca/content/view/65/29/ (03/03/2013 - 16h50);

• http://www.marfan.ca/content/view/65/29/ (01/03/2013 – 15h35);

• http://www.marfan.ca/content/view/66/30/ (03/03/2013 – 17h30);

• http://www.marfan.ca/content/view/67/31/ (02/03/2013 – 19h27);

• http://www.marfan.ca/content/view/68/32/ (02/03/2013 – 19h43);

• http://www.marfan.ca/content/view/69/33/ (04/03/2013 - 9h53);

• http://www.marfan.com.br/vivendo_marfan/asp_cardiologico/aspectocardio.asp?area=3&subarea=3_1 (01/03/2013 – 15h31)

• http://www.marfan.com.br/sobre_marfan/afeta/alt_cardiovascular/cardiovasculares.asp?area=1&subarea=1_3&subarea2=1_3_1 (03/03/2013 – 15h56)

• http://www.marfan.com.br/sobre_marfan/afeta/alt_ortopedicas/ortopedicas.asp?area=1&subarea=1_3&subarea2=1_3_2 (01/03/2013 – 15h47)

• http://www.marfan.com.br/sobre_marfan/sindrome/sindromemarfan.asp?area=1 (01/03/2013 – 15h43)

• http://www.marfan.com.br/pesquisas_tratamento/pesquisas/ace_inibitor.asp?area=2 (28/02/2013 - 17h20)

• http://www.marfan.com.br/pesquisas_tratamento/tratamento/tratamento.asp?area=2 (28/02/2013 - 17h18)

• http://www.marfan.com.br/vivendo_marfan/alimentacao/alimentacao.asp?area=3 (28/02/2013 - 17h14)

• http://www.marfan.com.br/vivendo_marfan/exercicios/dicas/atividadesdicas.asp?area=3&subarea=3_2 (28/02/2013 - 17h)

• http://www.marfan.com.br/vivendo_marfan/gravidez/gravidez.asp?area=3 (28/02/2013 - 17h16)

• http://www.marfan.org/marfan/2415/Treatment (04/03/2013 - 10h04)

• http://www.marfan.org/marfan/2324/What-to-Expect (04/03/2013 - 10h05)

• http://www.medicinenet.com/marfan_syndrome/page4.htm#what_types_of_doctors_treat_marfan_syndrome (01/03/2013 - 16h30)

• http://www.medicinenet.com/marfan_syndrome/page4.htm#what_treatment_options_are_available_for_marfan_syndrome (01/03/2013 - 16h40)

• http://www.medicinenet.com/marfan_syndrome/page5.htm#what_are_some_of_the_emotional_and_psychological_effects_of_marfan_syndrome (01/03/2013 - 16h43)

• http://www.ncbi.nlm.nih.gov/books/NBK1335/ (04.03.2013 – 10h17)

• http://www.ncbi.nlm.nih.gov/pubmed/23444230 (01/03/2013 – 15h32)

• http://www.ncbi.nlm.nih.gov/pubmed/23444230 (01/03/2013 – 15h35)

• http://www.nejm.org/doi/pdf/10.1056/NEJM197204132861502 (4/03/2013 - 9h46)

• http://www.news-medical.net/health/Marfan-Syndrome-Symptoms-(Portuguese).aspx (03/03/2013 – 15h50)

• http://www.nhs.uk/Conditions/Marfan-syndrome/Pages/Introduction.aspx (02/03/2013 - 17h17)

• http://www.nhs.uk/Conditions/Marfan-syndrome/Pages/Diagnosis.aspx (02/03/2013 - 17h35)

• http://www.nhs.uk/Conditions/Genetics/Pages/genetic-testing-and-counselling.aspx (02/03/2013 - 17h44)

• http://www.sciencedaily.com/releases/2006/04/060412093802.htm (04/03/2013 - 9h52)