10:23am Monday 21 August 2017

Researchers studying hereditary illnesses of peripheral nervous system make important discovery

Peripheral neuropathies
Hereditary peripheral neuropathies affect one in every 2,500 people. The most common disorder is Charcot-Marie-Tooth (CMT) disease. In the initial stages, it causes weakness and muscle loss in the lower legs, leading to walking difficulties. Eventually, sufferers will also likely experience weakness in the hands in the later stages of the disease.

The different types of peripheral neuropathies can be recognized based on their clinical and electrophysiological characteristics, but it remains difficult in most cases to determine their molecular genetic cause.  Many of the genes involved in these disorders have yet to be identified.

Mutations in the HINT1 gene
Magdalena Zimon and Jonathan Baets, under the supervision of Albena Jordanova and Peter De Jonghe, examined 33 CMT families. This study resulted in the identification of eight different mutations in the gene responsible for the production of the ‘histidine triad nucleotide-binding protein 1’ (HINT1). What especially drew the researchers’ attention was the fact that CMT patients with mutations in this gene displayed an untypical symptom of myotonia. Myotonia is characterized by the slow relaxation of muscles following voluntary exertion.  Hypersensitivity of the nerve or muscle is likely in the origin of this phenomenon. All HINT1 families pass on the disease as a recessive trait. This means that it occurs in a single generation with the parents of the patients showing no symptoms.

Diagnosis of peripheral neuropathies
The study makes a contribution to the development of better diagnostic tools for peripheral neuropathies and conditions accompanied by myotonia. It also demonstrates that HINT1 protein plays an important role in the functioning of the peripheral nervous system.  Unfortunately, it is at present still unclear how mutations in the HINT1 gene cause peripheral neuropathies associated with myotonia.

Relevant scientific paper

The paper was published in the leading journal Nature Genetics (Zimon et al., Loss of function mutations in HINT1 cause axonal neuropathy with neuromyotonia).

Research team
This study was conducted by the research groups of Albena Jordanova and Peter De Jonghe at the VIB Department of Molecular Genetics headed by Christine Van Broeckhoven, University of Antwerp.
Financial support
Financial support for this study was provided by Association Belge contre les Maladies neuro-Musculaires (ABMM), FWO, University of Antwerp and VIB.

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