Marfan Syndrome

Bibiliography

Dietz, H. C. M. (2011, December 1).

Marfan syndrome. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK1335/

Fbn1. (2013, December 3). Retrieved

from http://ghr.nlm.nih.gov/gene/FBN1

Learning about marfan syndrome. (2012,

November 14). Retrieved from http://www.genome.gov/19519224

MAHAJAN, AMBICAM C. M. (2013). Famous

people with marfan syndrome. Retrieved from http://www.mymagicmix.com/famous-people-with-marfan-syndrome/

Marfan syndrome. (2013, December 3).

Retrieved from http://ghr.nlm.nih.gov/condition/marfan-syndrome

What is marfan syndrome?. (2013).

Retrieved from http://www.marfan.org/about/marfan

Evolution

The only evolutionary benefit that can be linked with Marfan syndrome is the increase in height.

Genetics

Though this evolutionary adaptation succeeds in increasing the height of the individual, it comes with the unfortunate side-effect of severe organ malformations, resulting in earlier death.

Manifestations of Marfan Syndrome

Marfan Syndrome is inherited in an autosomal dominant pattern in 3 out of 4 people. At least 25% of cases result from a new spontaneous mutation, not inherited from their parents.

Age Factor

It is a systemic disorder of the connective tissue.

The Symptoms

This bar graph shows how some of the symptoms occur later in life. I would guess that some of the ones on the right are effected by treatment or death.

It has a high degree of clinical variability, meaning that you can show only some of the symptoms, you do not have to show all of them.

A Broad Phenotype

Not everyone with Marfan Syndrome has the same features and some features occur later in life.

The most common organs affected are the eye, skeleton and the cardiovascular system, especially the aorta and heart.

This bar graph shows the large variety of different symptoms that someone with Marfan Syndrome can have.

Marfan Syndrome is not always inherited, but it is always heritable.

Haploinsufficiency is sufficient to cause Marfan Syndrome.

Prevalence of Marfan Syndrome

World-wide Prevalence

Occurs in 1:5000 to 1:10,000 individuals.

Occurs in 0.02 % of the world population.

There is no apparent ethnic or racial group preference and no gender preference

There is no locality preference.

Sex-Linked Genes

Traits come from genes on the sex chromosomes. Men cannot be heterozygous dominant, so they have a greater chance of getting the recessive trait. Women are less likely to show the trait because they can be carriers.

Incomplete Dominance

The mixing of phenotypes due to intermediate inheritance. The phenotype is somewhere in between the two parent phenotypes.(Red x White = Pink). The dominant allele does not completely suppress the recessive allele.

Since the Marfan allele is dominant, if just one parent is heterozygous and the other is homozygous recessive(no Marfan), then theoretically 50% of their children will have Marfan Syndrome(will be heterozygous). If both parents are heterozygous, then 75% of their children would get Marfan Syndrome(25% homozygous dominant:50% heterozygous). If either parent is homozygous dominant for Marfan syndrome, then 100% of the children will have Marfan Syndrome.

Codominance

One gene has more than one dominant allele.

The Marfan Syndrome trait is inherited in an autosomally, like any basic Mendelian genetics.

Both of the phenotypes are expressed like in human blood.

Though it is not the case in Marfan Syndrome, there are deviations from Mendel's model. These deviations include Codominance, Incomplete Dominance, and Sex-Linked.

Marfan Syndrome

DNA

Marfan Syndrome is caused by a mutation of the FBN1 gene, also known as fibrillin 1.

Researchers have identified more than 1000 FBN1 gene mutations.

Causes of DNA Deviation

Change in DNA

As far as researchers are aware, 100% of Marfan Syndrome mutations are caused by a genetic defect.

Most mutations in Marfan syndrome change a single amino acid in the fibrillin-1 protein. This change affects the formation of the protein, and causes organs and structures of the body to change in unfortunate ways.

Types of Mutations

However, some researchers are looking at the environmental link between copper deficiency and Marfan Syndrome.

There are multiple types of mutations in FBN1.The mutation can be caused by deletions and insertions. The many mutations include nonsense and missense mutations, splice-site mutations, promoter mutations, etc.

Cell Biology

Marfan Syndrome's effect on the function of healthy cells.

Fibrillin-1 protein

Transforming Growth Factor-beta

Cell Dysfuction due to Marfan Syndrome

This protein is transported out of cells into the extra-cellular matrix and binds with other fibrillin-1 proteins to form a thread-like filament called microfibrils.

Controls growth the division of cells, cell motility, cell differentiation and cell death.

The FBN1 gene mutations either reduce the amount of fibrillin-1 produced (which alters its structure so that it is ineffective), or affects the transport of fibrillin-1 out of the cells.

Microfibrills store and regulate the availability the Transforming Growth Factor Beta (TGF-b),

TGF-beta is inactive when stored in the microfibrils and active when released from the microfibrils.

Meiosis

Mitosis

TGF-beta causes much more rapid cell division.

Heritable information is passed to the next generation. Four zygotes are formed.

To0 many growth cells produced.

The gene is located on chromosome 15 at position 21.1, from base pair 48,700,502 to base pair 48,937,984.

Severe reductions in fibrillin-1

Excess TGF-beta Growth Factors

Leads to overgrowth, less elasticity and instability of connective tissue.

Not enough normal amounts of Microfibrils are formed.

Less microfibrils to store and regulate TGF-beta proteins.

This is a problem with cell division, in the sense that the cells are dividing much more frequently than cells in someone without Marfan.

Excess TGF-beta growth factors are activated

Marfan Syndrome in History

Named after Antoine Marfan, a French Pediatrician, who in 1896 first described the condition in a 5 year old girl.

Osama Bin Laden?

He had some symptoms of Marfan Syndrome.

Musicians & Composers

Akhenaten?

Micheal Phelps?

Niccolo Paganini, Sergei Rachmaninoff, Jonathan Larson, Robert Johnson & Sir John Tavener.

Many people believe that Micheal Phelps has Marfan Syndrome.

He has been tested many times, especially as a child, and he does not have Marfan Syndrome.

Egyptian Pharaoh of 18th dynasty, may have had Marfan Syndrome.

President Abraham Lincoln?

Video

Was thought to have Marfan Syndrome based on skeletal characteristics.

Geneticists today doubt that he had Marfan Syndrome due to a history of normal eyesight and a lack of history of cardiovascular problems.