Senataxin mutations and amyotrophic lateral sclerosis

Abstract

We studied three patients with mutations in the senataxin gene (SETX). One had juvenile onset of ALS. The second case resembled hereditary motor neuropathy. The third patient had an overlap syndrome of ataxia-tremor and motor neuron disease, phenotypes previously associated with SETX mutations. Our patients were all apparently sporadic, with no other affected relative. Two relatives of patient no. 2 carried the SETX c.4660T > G transversion but did not manifest motor neuron disease, abnormal eye movements, ataxia, or tremor suggesting that genetic or environmental modifiers may influence expression of this SETX polymorphism. Relatives of patients 1 and 3 were not available for examination or SETX mutation screening. Mutations causing ALS4 may be more frequent and heterogeneous than expected. Screening for SETX mutations should be considered in patients with apparently sporadic juvenile-onset ALS, hereditary motor neuropathy, and overlap syndromes with ataxia and motor neuron disease.

Key words::

• Amyotrophic lateral sclerosis
• senataxin
• mutation
• ALS4
• genetics

Acknowledgements

MH and CMQ are supported by grants from the NIH, Muscular Dystrophy Association, and by the Marriott Mitochondrial Disorder Clinical Research Fund.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.