A novel locus for late onset amyotrophic lateral sclerosis/motor neurone disease variant at 20q13.

M otor neurone disease includes a heterogeneous group of disorders with motor neurone involvement, such as amyotrophic lateral sclerosis, progressive muscular atrophy, progressive bulbar palsy, and primary lateral sclerosis. Amyotrophic lateral sclerosis is the most common adult onset form of motor neurone disease and involves the lower and upper motor neurones. It is characterised by progressive muscle weakness and atrophy, with fasciculations associated with hyperreflexia and spasticity. One of the proposed mechanisms for amyotrophic lateral sclerosis is degeneration of the motor neurone because of abnormal levels of toxic products that accumulate in the cell. Death usually occurs by respiratory failure about 2–3 years after the first symptoms. About 10% of cases are familial amyotrophic lateral sclerosis, and several loci have been associated with this disease. To date, the only two genes identified have been the zinc–copper superoxide dismutase 1 (SOD1) gene, which is located on chromosome 21 (ALS1, MIM105400), and the Alsin gene, which is located at 2q33 (ALS2, MIM 205100). Autosomal dominant forms of amyotrophic lateral sclerosis also have been linked to 18q21 (ALS3, MIM 606640), 9q34 (ALS4, MIM 602433), and 15q15.1–q21.1 (ALS5, MIM 602099) and amyotrophic lateral sclerosis–frontotemporal dementia (MIM 105550) to 9q21-22. Moreover, mutations in Dynein are associated with motor neurone degeneration and defects in retrograde transport. This gene acts in the cellular division, trafficking, and transport of several proteins, such as SOD1. 11 More recently, two new loci have been associated with amyotrophic lateral sclerosis. One of them, reported by three independent groups, is on chromosome 16; the other is at 20p. We report a Caucasian Brazilian family with 26 members distributed in three generations affected by a late onset autosomal dominant motor neurone disease. Clinical and neurological examination of 11 living members was compatible with the diagnosis of Caucasian amyotrophic lateral sclerosis and motor neurone disease and long survival.