Mutated gene responsible for three forms of leukodystrophies has been identified by scientists. Leukodystrophies is a group of neurodegenerative disorders.
Mutations in this gene were identified in individuals from around the world but one mutation occurs more frequently in French-Canadian patients from Quebec.
The findings are crucial to the development of diagnostic tests and genetic counselling for families, and provide insights into a new mechanism for these disorders of the brain.
Currently, there are no cures for leukodystrophies, which are a group of inherited neurodegenerative disorders affecting preferentially the white matter of the brain.
White matter serves to cover nerve cell projections called axons, allowing nerve impulses to be correctly transmitted.
The study identified the first mutations in the POLR3A gene in families from Quebec. Mutations in the same gene were found in patients from the USA, Syria, Guatemala, France, and other European countries.
The international team was led by Drs Bernard Brais and Genevieve Bernard and included scientists from Montreal, Washington D.C., Dallas, Beirut, Paris, Clermont-Ferrand, and Bordeaux.
The group was able to demonstrate that mutations in the same POLR3A gene localized on chromosome 10 were responsible for three clinically different forms of leukodystrophies: Tremor-Ataxia with Central Hypomyelination (TACH) first described in Quebec cases, Leukodystrophy with Oligodontia (LO), and 4H syndrome or Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism syndrome.
"We identified many different mutations in the POLR3A gene which codes for a key subunit of RNA Polymerase III (Pol III), a highly conserved protein complex with a crucial role in gene expression, and many other important pathways," Dr. Brais explained.
"This finding is surprising considering the fundamental role of Pol III. It is also an encouraging discovery because if we can identify which targets of Pol III, when decreased, lead to the disease, we could develop therapeutic strategies to replace them," he stated.
The findings have been published in the September issue of the American Journal of Human Genetics.