SCIENTIFIC BACKGROUND

FXN

Scientific Background

Friedreich ataxia (FRDA1) is the most common autosomal recessive inherited ataxia with a prevalence of approximately 1:20,000 (in Southwestern Europe) to 1:250,000 (in Northern and Eastern Europe). First symptoms usually appear before the age of 20. The main symptoms include progressive gait ataxia, dysarthria, nystagmus, hollow high-arched foot feet (Friedreich's foot), predominantly sensory neuropathy with abnormalities in electrophysiology, lack of muscular reflexes, and pyramidal path tract signs. Initially, hypertrophic cardiomyopathy is often seen, later dilated cardiomyopathy is also observed. In the course of the disease initially hypertrophic, later also dilated cardiomyopathy is often observed. Not infrequently, visual acuity is impaired by optic atrophy, while hearing impairment is observed in less than 10%. Cognitive abilities are usually not impaired, and about 30% of those affected develop diabetes mellitus. Neuropathological findings include evidence of degeneration of the dorsal pathways, the spinocerebellar tract and the sensory neurons of the dorsal root cells. Death usually occurs in the 4th decade of life, often as a result of cardiomyopathy or impaired brain stem functions.

 

The disease is caused by a GAA triplet repeat expansion in intron 1 of the FXN gene. Normal persons have about 7-33 GAA repeats. In healthy premutation carriers, 34-65 uninterrupted GAA triplets can be detected, which may be extended when passed on to the next generation. Patients have 66 to about 1,700 repeats. In more than 95-98% of cases the disease is caused by two alleles with the GAA triplet repeat expansion, while in about 2-3% the cause is expansion on one allele and a point mutation, more rarely a deletion, on the other FXN allele. GAA expansion reduces the expression of frataxin, a protein involved in mitochondrial iron homeostasis.

 

References

Cook et al. 2017, Br Med Bull.; 124:19 / Bürk, 2017, Cerebellum Ataxias; 4: 4 / Schulz et al. 2009, Nat Rev Neurol 5:222 / Pandolfo et al. 2009, J Neurol 256:Suppl 1 / Wilson 2006, Semin Pediatr Neurol 13:166 / Delatycki et al. 2000, J Med Genet 37:1 / Montermini et al. 1997, Hum Mol Genet 6:1261 / Dürr et al. 1996, New Eng J Med 335:1169 / Campuzano et al. 1996, Science 271:1423

GENES

FXN

ASSOCIATED TESTS

How to order

LATEST ARTICLES

Have you ever wondered how jet-setting across the globe might affect your gut health? A recent study has dug into this intriguing question, revealing...

Read more

In June 2023, Medicover Genetics attended the 56th conference of the European Society of Human Genetics (ESHG) which took place in Glasgow, Scotland....

Read more

Vitamin D, also known as “the sunshine vitamin”, is a fat-soluble vitamin that helps the body absorb calcium and phosphate, which are essential f...

Read more

Every movement our body makes is controlled by a long, thin, tube-like structure called the “spinal cord”. The spinal cord is part of our nervous...

Read more

Genetic variant databases are vital for interpreting genetic variations in clinical settings and research. However, misclassified variants can create...

Read more

A recent article published by our team in the International Journal of Molecular Sciences [1], aimed to evaluate the prevalence, prognostic and predi...

Read more

A healthy, nutritious and well-balanced diet is always important for a person’s well-being, and it is even more so during pregnancy as the developi...

Read more

The sun is hot and you are sweating. Most of us know how it feels to sweat, and when we sweat. This is a normal bodily response to an increase in tem...

Read more

All about the pancreas The pancreas is a pear-shaped organ that is located at the upper left side of the abdomen, behind the stomach. It has two m...

Read more

The father of genetics is Gregor Mendel. Mendel was an Austrian monk, whose experiments breeding pea plants in the monastery garden led to breakthrou...

Read more