Analysis of the UNC13A gene as a risk factor for sporadic amyotrophic lateral sclerosis.

A myotrophic lateral sclerosis (ALS) is an adultonset neurodegenerative disease characterized by progressive loss of motor neurons from the spinal cord, brainstem, and cerebral cortex that typically results in death 2 to 5 years following onset. Approximately 10% of patients with ALS have a family history, of which 15% to 20% are linked to mutations in the SOD1 gene; these patients most frequently inherit the disease in an autosomal dominant manner. Mutations in other genes including ALS2, ANG, DCTN1, SETX, VAPB, TARDBP, and FUS have also been reported in familial cases. The remaining 90% of cases have no obvious family history and are referred to as sporadic ALS (SALS). The etiology of these sporadic cases is considered multifactorial, with environmental and genetic factors contributing to disease susceptibility. Although candidate gene studies have identified potential risk factors for SALS, replication of these associations in different populations have often failed. Similarly, several genome-wide association studies for SALS have identified novel candidate susceptibility genes including ITPR2, FGGY, and DPP6; however, these associations have not been consistently replicated. Recently, a large-scale genome-wide association study that included 19 838 subjects showed that the variant rs12608932 located in the unc-13 homologue A gene (UNC13A) is strongly associated with SALS. The aim of this study is to investigate the variant as a possible risk factor for developing ALS in a French population.