SQSTM1 mutations in Han Chinese populations with sporadic amyotrophic lateral sclerosis

Mutations in the sequestosome 1 gene (SQSTM1) have recently been identified in patients with amyotrophic lateral sclerosis, accounting for 1.11%–4.92% of familial ALS and 2.42%–4.37% of sporadic amyotrophic lateral sclerosis (SALS). The mutation spectrum of SQSTM1 in Chinese patients with SALS remains unknown. Three hundred and six patients with SALS from the Department of Neurology, West China Hospital of Sichuan University were recruited for this study. From the same region, 350 healthy individuals were recruited as a control group. The encoding regions of SQSTM1 were screened by direct sequencing. Three novel nonsynonymous mutations— p. I99L, p. D337E, and p. L341V—were identified in 3 patients with SALS, none of which were found in healthy controls. The male patient carrying mutation p. I99L presented limb symptom at age of 34 and died in 34 months. Two late-onset patients carrying D337E and p. L341V mutations had bulbar and limb onset, respectively. Moreover, a c.1166-14_1166-11delTACT mutation in the intron 7 was found in a living male patient with limb onset at age of 62. None of the patients carrying SQSTM1 mutation showed clinical evidence of concomitant Paget disease of bone or mutation of the valosin-containing protein gene. The mutation frequency of SQSTM1 was 0.98% in Chinese patients with SALS, which was lower than those in other racial populations.