The location and genetic conservation of the mutations in <i>UBQLN2</i> gene.

<p>(A) Ubiquilin-2 protein indicating structural and functional domains: UBL (ubiquitin-like domain), STI1 (heat-shock-chaperonin binding motif), PXX (proline-rich region) and UBA (ubiquitin-associated domain). Our detected mutations are displayed in red. (B) The conservation of ubiquilin-2 protein in different species. The mutated residues are displayed in red.</p

Table_1_Immune-mediated diseases are associated with a higher risk of ALS incidence: a prospective cohort study from the UK Biobank.docx

ObjectiveThe occurrence of immune-mediated diseases (IMDs) in amyotrophic lateral sclerosis (ALS) patients is widely reported. However, whether IMDs and ALS is a simple coexistence or if there exists causal relationships between the two has been a subject of great interest to researchers.MethodsA total of 454,444 participants from the prospective cohort of UK Biobank were recruited to investigate the longitudinal association between IMDs and ALS. Previously any IMDs and organ specific IMDs were analyzed in relation to the following incident ALS by Cox-proportional hazard models. Subgroup analyses were performed to explore the covariates of these relationships.ResultsAfter adjusting for potential covariates, the multivariate analysis showed that any IMDs were associated with an increased risk of ALS incidence (HR:1.42, 95%CI:1.03-1.94). IMDs of the endocrine-system and the intestinal-system were associated with increased risk of ALS incidence (endocrine-system IMDs: HR:3.01, 95%CI:1.49-6.06; intestinal system IMDs: HR:2.07, 95%CI: 1.14-3.77). Subgroup analyses revealed that immune burden, including IMD duration and the severity of inflammation had specific effects on the IMD-ALS association. In participants with IMD duration≥10 years or CRP≥1.3mg/L or females, previous IMDs increased the risk of incident ALS; however, in participants with IMD duration InterpretationOur study provides evidence that previous any IMDs and endocrine-system and the intestinal-system specific IMDs are associated with an increased risk of developing ALS in females, but not in males.</p

Identification of an A4V SOD1 mutation in a Chinese patient with amyotrophic lateral sclerosis without the A4V founder effect common in North America

<p>We identified a missense alanine to valine mutation at codon 4 (A4V) in the Cu/Zn superoxide dismutase (SOD1) gene in a 51-year-old male of Chinese origin with familial amyotrophic lateral sclerosis (ALS). The patient displayed a typical A4V-related phenotype that included rapid progression and predominant lower motor neuron involvement. This patient is the first such carrier reported outside Caucasian ALS patients, despite the fact that A4V mutations account for up to 50% of all SOD1 mutations in North America. Further SNP analyses showed that the A4V patient of Chinese origin did not share the common founder effect observed in North America.</p

Data_Sheet_1_Screening for CCNF Mutations in a Chinese Amyotrophic Lateral Sclerosis Cohort.PDF

<p>Previous research has identified CCNF mutations in familial (FALS) and sporadic amyotrophic lateral sclerosis (SALS), as well as in frontotemporal dementia (FTD). The aim of our study was to measure the frequency of CCNF mutations in a Chinese population. In total, 78 FALS patients, 581 SALS patients and 584 controls were included. We found 19 missense mutations, nine synonymous mutations and two intron variants. According to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines for the interpretation of sequence variants, eight variants were judged to be pathogenic or likely pathogenic variants. The frequency of such variants was 2.56% in FALS and 1.03% in SALS. In conclusion, CCNF mutations are common in FALS and SALS patients of Chinese origin, and further study is still needed.</p

Performances in cognitive scores and ECAS time of ALS patients and healthy controls.

<p>Performances in cognitive scores and ECAS time of ALS patients and healthy controls.</p

Alignment of human dynactin subunit 1 (isoform 1) amino acid sequences from different species.

<p>The p.R623W variant was conserved in mammals, p.A933V variant was conserved in vertebrata.</p

Amendments in the Chinese version compared to the original English version.

<p>Amendments in the Chinese version compared to the original English version.</p

Characteristics of participants: ALS patients and healthy controls.

<p>Characteristics of participants: ALS patients and healthy controls.</p

Correlations between the scores of ECAS and other neuropsychological tests.

<p>Correlations between the scores of ECAS and other neuropsychological tests.</p

Abnormal cut-off scores and frequency of patients with cognitive impairments.

<p>Abnormal cut-off scores and frequency of patients with cognitive impairments.</p