Marfan Syndrome: Unraveling the Genetic Link to Connective Tissue
Marfan syndrome is a genetic disorder that impacts connective tissue, the supportive material found throughout the human body. This tissue provides strength, flexibility, and structure to various organs and systems.
The FBN1 Gene
The gene responsible for Marfan syndrome is known as FBN1. This gene contains the instructions for producing a protein called fibrillin-1. Fibrillin-1 is a key component of microfibrils, which are thread-like structures that assemble to form elastic fibers.
These elastic fibers are integral to the extracellular matrix, a complex network of proteins and other molecules that surrounds and supports cells within tissues. Fibrillin-1 contributes to the structural integrity and elasticity of tissues found in various parts of the body, including the skin, ligaments, and blood vessels. When mutations occur in the FBN1 gene, the body produces abnormal fibrillin-1, which is the direct cause of Marfan syndrome.
Location on Chromosome 15
The FBN1 gene is located on chromosome 15. Humans have 23 pairs of chromosomes, which carry our genetic information. Chromosome 15 is an autosome, meaning it is one of the non-sex chromosomes. More precisely, the FBN1 gene resides at a specific band on the long arm, or ‘q’ arm, of chromosome 15, designated as 15q21.1.
How Marfan is Inherited
Marfan syndrome follows an autosomal dominant inheritance pattern. This means an individual only needs to inherit one copy of the altered FBN1 gene from a parent to develop the condition. If one parent has Marfan syndrome, there is a 50% chance that each child will inherit the mutated gene and thus the condition.
Approximately 75% of Marfan syndrome cases are inherited from an affected parent. However, in about 15% to 30% of cases, the condition arises from a new, spontaneous genetic mutation that occurs for the first time in the affected individual, with no family history of the disorder.
Consequences of the Gene Mutation
Mutations in the FBN1 gene lead to the production of defective fibrillin-1 protein. This abnormal fibrillin-1 weakens the connective tissue throughout the body, compromising its ability to provide proper support and elasticity.
Fibrillin-1 also plays a role in regulating growth factors, such as transforming growth factor-beta (TGF-β). When fibrillin-1 is abnormal, it can lead to an increase in the activity of TGF-β, which further contributes to the degradation and disorganization of connective tissue. This widespread weakening of connective tissue can impact the integrity of various body systems, including the cardiovascular system, skeletal system, and eyes.