AUTHOR=Hou Xiaorong , Li Wanzhen , Liu Pan , Liu Zhen , Yuan Yanchun , Ni Jie , Shen Lu , Tang Beisha , Wang Junling 

TITLE=The Clinical and Polynucleotide Repeat Expansion Analysis of ATXN2, NOP56, AR and C9orf72 in Patients With ALS From Mainland China

JOURNAL=Frontiers in Neurology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.811202

DOI=10.3389/fneur.2022.811202

ISSN=1664-2295

ABSTRACT=<sec><title>Background</title><p>Repeat expansions, including those in <italic>C9orf72</italic> and <italic>ATXN2</italic>, have been implicated in amyotrophic lateral sclerosis (ALS). However, there have been few studies on the association of <italic>AR</italic> and <italic>NOP56</italic> repeat expansion with ALS, especially in China. Accordingly, we aimed to evaluate the frequency of <italic>C9orf72</italic> and <italic>ATXN2</italic> repeat mutations and investigate whether <italic>NOP56</italic> and <italic>AR</italic> repeat expansion are risk factors for ALS.</p></sec><sec><title>Methods</title><p>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 <italic>C9orf72, ATXN2, AR</italic>, and <italic>NOP56</italic>.</p></sec><sec><title>Results</title><p>GGGGCC repeats in <italic>C9orf72</italic> 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 (<italic>p</italic> = 0.006). Regarding <italic>ATXN2</italic> CAG repeats, we identified that intermediate repeat lengths (29–34 copies) were associated with ALS (<italic>p</italic> = 0.033), and there was no difference in clinical characteristics between the groups with and without intermediate repeats (<italic>p</italic> &gt; 0.05). Meanwhile, we observed that there was no association between the repeat size in <italic>AR</italic> and <italic>NOP56</italic> and ALS (<italic>p</italic> &gt; 0.05).</p></sec><sec><title>Conclusions</title><p>Our results demonstrated that pathogenetic repeats in <italic>C9orf72</italic> are rare in China, while intermediate CAG repeats in <italic>ATXN2</italic> are more frequent but have no effect on disease phenotypes; the repeat size in <italic>AR</italic> and <italic>NOP56</italic> may not be a risk factor for ALS.</p></sec>