Scientists find why an enervating disorder affects only Eurasians, Pg II

Key Highlights:

• Friedreich’s ataxia (FRDA) is a genetic disorder causing progressive damage to nerves and the heart, typically appearing between ages 5 and 15.
• The disorder is caused by a mutation in the FXN gene, which codes for the protein frataxin, essential for mitochondria function.
• A new study published in Human Molecular Genetics found that FRDA primarily affects individuals of Eurasian descent, including European, North African, West Asian, and South Asian populations.
• The research identified that the expanded variants causing FRDA originated from two specific long-normal variants, both mutating in Eurasia at two historical points.
• In India, Nizam’s Institute of Medical Sciences diagnoses one FRDA case monthly, predominantly linked to consanguineous marriages.

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Detailed Insights:

• Individuals with FRDA experience impaired coordination, slurred speech, difficulty swallowing, vision/hearing deterioration, and fatigue.
• The FXN gene mutation involves an abnormal expansion of repeat sequences within its intron, leading to reduced frataxin production.
• Low frataxin levels impair mitochondria's ability to produce ATP, the cell's energy currency, causing cellular dysfunction.
• The absence of FRDA in sub-Saharan Africa and East Asia is attributed to the lack of these specific long-normal variants or the historical mutation events.
• Protomutations, which are non-disease-causing but abnormal variants, acted as reservoirs, slowly expanding into disease-causing variants over generations.
• Ancient DNA analysis revealed these two protomutations were present in Europe and Western Asia at least 9,000 years ago.

Scientific/Technical Concepts Involved:

• Friedreich’s ataxia: A progressive, neurodegenerative genetic disorder affecting the nervous system and heart.
• FXN gene: The specific gene whose mutation causes Friedreich’s ataxia by affecting frataxin production.
• Frataxin: A protein crucial for the proper functioning of mitochondria, involved in energy production.
• Mitochondria: Often called the "powerhouses" of the cell, responsible for generating most of the cell's supply of ATP.
• ATP: Adenosine triphosphate, the main energy currency of the cell, used for various cellular processes.
• Protomutations: Originator mutations that are non-disease-causing but can expand into disease-causing variants over time.