Progeria: The Genetics of Accelerated Aging

Summary

In this webinar, medical genomics students from the University of Toronto delve into Hutchinson-Gilford Progeria syndrome, a rare genetic disorder causing accelerated aging in children. They explain the condition's genetic basis, detailing how a mutation in the LMNA gene leads to the production of a defective protein, progerin, which destabilizes cellular structures and accelerates aging. The presentation covers symptoms, the impact on cell division, and current treatment approaches, including the promising Lonafarnib Monotherapy. The session concludes with a quiz to test viewers' understanding of Progeria.

Takeaways

• 🌟 Progeria, also known as Hutchinson-Gilford Progeria syndrome (HGPS), is a rare genetic disorder that leads to accelerated aging in children.
• 🧬 The condition is caused by a mutation in the LMNA gene, which results in the production of a defective protein called progerin.
• 🧬 Progeria is an autosomal dominant disorder, meaning that only one mutated gene copy is needed to cause the disease.
• 🔬 The LMNA gene mutation involves a point mutation where a Cytosine (C) is changed to a Thymine (T), leading to the creation of progerin instead of lamin A.
• 🧪 The mutation affects the splicing process of the LMNA gene, causing a deletion in the messenger RNA and the production of progerin, which is missing 50 amino acids compared to lamin A.
• 🧬 Progerin accumulation destabilizes the nuclear envelope and disrupts the normal functions of the cell, leading to premature aging and various health issues.
• 🧬 The average life expectancy for individuals with Progeria is 13 years, although some with milder forms of the disease can live into their 20s.
• 🌍 Progeria is extremely rare, affecting approximately 1 in 20 million people, with about 400 individuals living with the condition worldwide.
• 🏥 There is currently no cure for Progeria, but management strategies include medical counseling, specific diets, hearing aids, medications for heart problems, and orthopedic management.
• 💊 A new treatment, Lonafarnib Monotherapy, is in clinical trials and has shown promise in improving the lifespan and health outcomes for individuals with Progeria.

Q & A

What is Hutchinson-Gilford Progeria syndrome, also known as?

Hutchinson-Gilford Progeria syndrome is also known as Progeria, a rare genetic disorder that causes children to age rapidly.

What is the average life expectancy for a person with Progeria?

The average life expectancy for a person with Progeria is 13 years, although some individuals with milder forms of the disease may live into their 20s or beyond.

How common is Progeria, and what are some of its physical features?

Progeria affects 1 in 20 million people worldwide. Some physical features include stunted growth, a small lower jaw, thin lips, a beaked nose, hair loss, and thin, wrinkled skin with visible veins.

What are some of the physiological features associated with Progeria?

Physiological features of Progeria include hearing loss, delayed and abnormal tooth formation, severe progressive heart and blood vessel disease, loss of fat and muscle mass, fragile bones, and stiff joints.

How is Progeria diagnosed, and what causes it?

Progeria is diagnosed through a genetic test for LMNA gene mutations. The disorder is caused by mutations in the LMNA gene, which leads to the creation of a defective protein called progerin.

What is the role of the LMNA gene in the body, and how does it relate to Progeria?

The LMNA gene is responsible for creating lamin proteins, which are crucial for maintaining the structure of the cell nucleus. In Progeria, a mutation in the LMNA gene leads to the production of progerin, which destabilizes the nucleus and contributes to the rapid aging process.

How does the C to T mutation in the LMNA gene affect the production of lamin proteins?

The C to T mutation in the LMNA gene creates an accidental splice site in exon 11, leading to a deletion of 150 base pairs and the production of progerin instead of lamin A. Progerin is missing 50 amino acids compared to lamin A, which has significant effects on cellular function.

What is the function of lamin proteins in the cell, and how does progerin disrupt these functions?

Lamin proteins help package DNA into chromatin, bind to proteins involved in DNA replication and repair, and maintain the structure of the nucleus. Progerin, by displacing lamin from the nuclear lamina, destabilizes the nuclear envelope, leading to DNA damage and cellular stress.

What is the connection between progerin and DNA repair in Progeria?

In Progeria, progerin holds onto DNA repair proteins, preventing them from interacting with and repairing the DNA. This leads to an accumulation of DNA damage and contributes to cellular stress and premature aging.

What are some current treatment strategies for managing Progeria?

Current treatment strategies for Progeria include managing symptoms through a specific diet, hearing aids, medications for heart problems, frequent use of sunscreen, and orthopedic management for hip and muscle issues.

What is Lonafarnib Monotherapy, and how does it relate to Progeria treatment?

Lonafarnib Monotherapy is a new treatment undergoing human clinical trials for Progeria. It works by preventing progerin from accumulating in the nucleus membrane, leading to improvements in life span, bone strength, weight, blood circulation, and hearing in patients.