The Clinical and Polynucleotide Repeat Expansion Analysis of and in Patients With ALS From Mainland China.

BACKGROUND

Repeat expansions, including those in and , have been implicated in amyotrophic lateral sclerosis (ALS). However, there have been few studies on the association of and repeat expansion with ALS, especially in China. Accordingly, we aimed to evaluate the frequency of and repeat mutations and investigate whether and repeat expansion are risk factors for ALS.

METHODS

In this study, 736 ALS patients and several hundred healthy controls were recruited. Polymerase chain reaction (PCR) and repeat-primed PCR (RP-PCR) were performed to determine the repeat lengths in , and .

RESULTS

GGGGCC repeats in were observed in six ALS patients (0.8%, 6/736) but not in any of the controls (0/365). The patients with pathogenic GGGGCC repeats showed shorter median survival times than those with a normal genotype ( = 0.006). Regarding CAG repeats, we identified that intermediate repeat lengths (29-34 copies) were associated with ALS ( = 0.033), and there was no difference in clinical characteristics between the groups with and without intermediate repeats ( > 0.05). Meanwhile, we observed that there was no association between the repeat size in and and ALS ( > 0.05).

CONCLUSIONS

Our results demonstrated that pathogenetic repeats in are rare in China, while intermediate CAG repeats in are more frequent but have no effect on disease phenotypes; the repeat size in and may not be a risk factor for ALS.