Chinese Amyotrophic Lateral Sclerosis Patients Research Articles

Characteristics of Late-Onset Amyotrophic Lateral Sclerosis in a Chinese Cohort

Objective: This retrospective study analyzed the clinical characteristics and prognosis of the elderly amyotrophic lateral sclerosis (ALS) population in a large sample. Methods: The study included 1,005 patients with sporadic ALS admitted to Chinese PLA General Hospital between March 2011 and March 2021. We stratified the ALS patients into young and old groups using 2 cutoffs for the age at disease onset (≥65 or ≥70 years old) and compared their demographic, clinical, and survival data. Results: The mean onset age of all patients was 52.79 ± 10.55 years, with 123 (12.24%) having a disease onset ≥65 years and 44 (4.38%) having an onset ≥70 years. There were 624 (62.1%) male patients. More bulbar-onset cases were in the late-onset group (p = 0.001). The sex distribution, time from onset to diagnosis, and the time of symptom spread from spinal or bulbar localization to a generalized localization did not differ between groups. Late-onset patients progressed more rapidly and had a significantly shorter survival. Conclusions: Chinese ALS patients have an earlier age at onset and a relatively smaller proportion of old onset than European and Japanese patients. Elderly patients are more likely to have bulbar onset, which is related to rapid progression and a shorter survival.

GLT8D1 may not be significant in Chinese sporadic amyotrophic lateral sclerosis patients

To detect the mutation frequency of exon 4 of amyotrophic lateral sclerosis (ALS) in a new disease-causing gene, GLT8D1 (NM_018446), in Chinese patients, we used whole-exome sequencing technology to screen the full-length GLT8D1 gene in 539 Chinese sporadic ALS patients and 176 controls without a history of neurological diseases. Then, we sequenced the coding region of exon 4 in the GLT8D1 gene in a cohort consisting of 256 sporadic ALS patients. Our current results did not find an association between GLT8D1 and ALS in Chinese patients, and further studies will be required.

Rare variants of HSPB1 are probably associated with amyotrophic lateral sclerosis

To explore the association between rare HSPB1 variants and amyotrophic lateral sclerosis (ALS). We performed next-generation sequencing for 166 Chinese ALS patients to screen for possible pathogenic rare variants of HSPB1. The control individuals were obtained from 1000 Genome Project and an in-house whole-exome sequencing database. The Sequence Kernel Association Test (SKAT) and the SKAT-optimal test (SKAT-O) were used to identify the association between rare HSPB1 variants and ALS. We identified 3 possible pathogenic rare variants of HSPB1 (all were missenses), including c.379C>T (p.R127W), c.446A>C (p.D149A) and c.451A>C (p.T151P). Compared with 1000 Genome Project, SKAT p=3.61×10-7 and SKAT-O p=1.62×10-6; while compared with the in-house database, SKAT p=9.99×10-4, SKAT-O p= 1.80×10-3. We analyzed the phenotypes of rare HSPB1 variant carriers and found no specific clinical characteristics associated with these variants. Rare variants of HSPB1 are probably associated with the pathogenesis of ALS.

SQSTM1L341V variant that is linked to sporadic ALS exhibits impaired association with MAP1LC3 in cultured cells.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are genetically, pathologically and clinically-related progressive neurodegenerative diseases. Thus far, several SQSTM1 variations have been identified in patients with ALS and FTD. However, it remains unclear how SQSTM1 variations lead to neurodegeneration. To address this issue, we investigated the effects of ectopic expression of SQSTM1 variants, which were originally identified in Japanese and Chinese sporadic ALS patients, on the cellular viability, their intracellular distributions and the autophagic activity in cultured cells. Expression of SQSTM1 variants in PC12 cells exerted no observable effects on viabilities under both normal and oxidative-stressed conditions. Further, although expression of SQSTM1 variants in PC12 cells and Sqstm1-deficient mouse embryonic fibroblasts resulted in the formation of numerous granular SQSTM1-positive structures, called SQSTM1-bodies, their intracellular distributions were indistinguishable from those of wild-type SQSTM1. Nonetheless, quantitative colocalization analysis of SQSTM1-bodies with MAP1LC3 demonstrated that among ALS-linked SQSTM1 variants, L341V variant showed the significantly lower level of colocalization. However, there were no consistent effects on the autophagic activities among the variants examined. These results suggest that although some ALS-linked SQSTM1 variations have a discernible effect on the intracellular distribution of SQSTM1-bodies, the impacts of other variations on the cellular homeostasis are rather limited at least under transiently-expressed conditions.

Medical cost and healthcare utilization of amyotrophic lateral sclerosis in China: A cohort study based on hospital data from 2015 to 2018.

Amyotrophic lateral sclerosis (ALS), a specific neurodegenerative disease, imposed increased economic and utilizations burden on the healthcare system, especially with the progress of the diseases severity. However, the economic burden on Chinese ALS patients remained unclear. This study therefore was aimed to investigate medical cost and healthcare utilization for Chinese ALS patients.Longitudinal health data of over 20 million individuals, including military personnel and civilians, was collected from all Chinese military hospitals. We identified 480 patients with a first major diagnosis for ALS from 2015 to 2018, while matched 400 controlled patients on age, gender, ethnic group, geographic region, length of stay, year of diagnosis and comorbidity. Their medical cost and healthcare utilizations were then measured 1 year before, and 1 year after ALS diagnosis.The median annual medical cost of ALS patients was about 2-fold higher, 17,087 CNY during the index year than 1 year before, 7859 CNY. The highest increase in utilizations may account for medical costs on ALS patients, which was represented by hospitalizations (Odd Ratio (OR) = 4.26, 95% confidence interval (CI) 3.52, 5.15), electromyography (OR = 4.14, 95% CI 2.37, 7.22), nerve conduction velocity (OR = 3.26, 95% CI 2.23, 4.77).This study is the first one reporting direct economic burden on Chinese ALS patients. Efforts should be made to develop cost-effective diagnostic tools in order that sources of medical cost were more effectively allocated, and this disease was detected earlier.

Identification of novel FUS and TARDBP gene mutations in Chinese amyotrophic lateral sclerosis patients with HRM analysis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons. More than 30 genes have been linked to ALS to date, including FUS and TARDBP, which exhibit similar roles in RNA metabolism. This study explored the use of high-resolution melting (HRM) analysis to screen for FUS and TARDBP mutation hotspot regions in 146 Chinese ALS patients, which achieved 100% detection. Two FUS mutations were observed in two different familial ALS probands, a missense mutation (p.R521H) and a novel splicing mutation (c.1541+1G>A). Five TARDBP mutations were identified in six ALS patients, including a novel 3’UTR mutation (c.*731A>G) and four missense mutations (p.G294V, p.M337V, p.G348V, and p.I383V). We found that FUS mutations were present in 1.4% of Chinese ALS patients, whereas TARDBP mutations were responsible for 4.1% of Chinese ALS cases. Here, we describe the accuracy of using highly sensitive HRM analysis to identify two novel FUS and TARDBP mutations in Chinese sporadic and familial ALS cases. Our study contributes to the further understanding of the genetic and phenotypic diversity of ALS.

TBK1 variants in Chinese patients with amyotrophic lateral sclerosis

TBK1 has been reported as a risk gene of amyotrophic lateral sclerosis (ALS). We screened TBK1 variants in 69 familial ALS patients and 608 sporadic ALS patients from mainland China. All 20 coding exons and the exon–intron flanking regions of TBK1 were amplified and sequenced using Sanger sequencing. In total, we identified eight missense variants and one suspicious splice site mutation. The patient with K291R had a family history of ALS. Other variants were detected in sALS patients. Interestingly, 2 patients with variants in TBK1 carried another variant in other genes related to autophagy: G175S in TBK1 and P392L in SQSTM1; and D534H in TBK1 and E372D in SQSTM1. We concluded that TBK1 variants account for approximately 1.3% of Chinese ALS patients. Screening for this gene in ALS patients is necessary, especially in the group with variants in other genes related to the autophagy pathway.

Early onset but long survival and other prognostic factors in Chinese sporadic amyotrophic lateral sclerosis

ObjectivesTo explore the cause of long survival but early onset and other prognostic factors among Chinese sporadic amyotrophic lateral sclerosis (ALS) patients. MethodsPatients with ALS were recruited and followed up from Jan 2013 to Jan 2017. Phenotype and survival were compared among different age-at-onset groups. Candidate prognostic factors were analyzed by Kaplan-Meier method, Cox regression and Royston Parmar (RP) model dealing with breaches of proportional hazard assumption. ResultsIn the cohort of 531 patients, mean age-at-onset was 53.68 years (SD:10.85) and overall estimated median survival time was 59 months (95% CI: 48.29–69.71). Pairwise comparison showed that patients above 65 years at onset were more frequently bulbar onset (adjusted residual: 3.0), less frequently lumbosacral onset (adjusted residual: −3.0), and had shorter survival compared with other age groups (p = 0.002). Cox and RP model demonstrated independent prognostic variables including age at onset, bulbar onset, diagnostic delay, MRC-score at first diagnosis and region of residence. ConclusionsThis clinic-based study suggested that Chinese sporadic ALS patients had relatively long survival probably due to young age and less bulbar onset cases. Short diagnostic delay, low MRC-score and northern residence were also predicative of short survival. Reallocation of resources is needed to optimize quality care and prolong survival time.

Restless Legs Syndrome in Chinese Patients With Sporadic Amyotrophic Lateral Sclerosis.

Objective: To evaluate the frequency and clinical features of restless legs syndrome (RLS) in a group of Chinese patients with amyotrophic lateral sclerosis (ALS).Methods: 109 Patients included in this study fulfilled the revised El Escorial diagnostic criteria for clinically definite, probable and lab-supported probable ALS, and a group of 109 control subjects was matched for age and sex to the ALS group. Disease severity was assessed by the revised ALS functional rating scale (ALSFRS-R). The diagnosis of RLS was made according to the criteria of the International RLS Study Group. Other characteristics including sleep quality, excessive daytime sleepiness (EDS), REM sleep behavior disorder (RBD), depression and anxiety were also evaluated in ALS patients.Results: RLS was significantly more frequent in ALS patients than in control subjects (14.6 vs. 0.9%; P < 0.05). Compared to those without RLS, ALS patients with RLS reported a higher frequency of anxiety and EDS. ALS patients with RLS showed more severe legs dysfunction. EDS and legs function scores of the ALSFRS-R were independent factors significantly associated with RLS in ALS patients.Conclusions: Our findings suggest that Chinese ALS patients exhibit a high frequency of RLS symptoms and that these patients may benefit from recognition of the condition and optimized management of its symptoms. Moreover, ALS patients might cause circadian rhythms disturbance and our study further supports that ALS is a heterogeneous disorder involving multiple systems; further studies are needed to confirm these preliminary findings.

Mutation analysis of KIF5A in Chinese amyotrophic lateral sclerosis patients

Amyotrophic lateral sclerosis (ALS) is an age-related fatal neurodegenerative orphan disorder that is characterized by progressive injury of both the upper and lower motor neurons. Recently, loss-of-function mutations predominately disrupting the C-terminal amino acid sequence of KIF5A via aberrant exon 27 splicing have been reported in European ALS cohorts. However, the contributions of KIF5A mutations in Asian patients with ALS remain unclear. KIF5A sequences, including exons 26 and 27, were analyzed in a large Chinese ALS cohort comprising 33 unrelated familial ALS probands, 645 sporadic ALS (SALS) patients, 15 ALS patients presenting with concomitant frontotemporal dementia, 400 in-house controls, and 12,951 East Asian individuals from the Exome Aggregation Consortium and Genome Aggregation Database databases. As a result, the previously reported canonical splicing site mutation c.2993-1G>A was found in 1 SALS patient, while no mutations were detected in familial ALS case or ALS patients presenting with concomitant frontotemporal dementia. The frequency of KIF5A mutations accounts for 0.16% (1/645) of Chinese SALS patients, implying that it is an uncommon genetic determinant of ALS in Chinese patients.

Mutation screening of NEK1 in Chinese ALS patients.

NEK1 was recently identified as an amyotrophic lateral sclerosis (ALS) gene through rare variant burden analysis, and its role in ALS in various populations is still unclear. The aim of this study was to determine the frequency and spectrum of NEK1 mutations in an ALS cohort from mainland China. All exons and their flanking intron regions of NEK1 were screened by direct nucleotide sequencing in 377 unrelated ALS patients. These patients were also screened with a massive parallel sequencing gene panel for 24 known ALS genes and C9orf72 hexanucleotide repeat expansion. In totality, we detected 9 variants, comprising 3 novel heterozygous loss-of-function mutations and 6 rare missense variants (MAF < 0.1%) in NEK1. The patient with splice site mutation also carried another probably damaging variant in SOD1. Our study established a NEK1 mutant frequency of 0.8% in Chinese ALS patients, further expanded its spectrum of variants, and highlighted the possibility of coexistence with variants in additional ALS genes in NEK1 loss-of-function carriers.

ANXA11 mutations prevail in Chinese ALS patients with and without cognitive dementia.

ObjectiveTo investigate the genetic contribution of ANXA11, a gene associated with amyotrophic lateral sclerosis (ALS), in Chinese ALS patients with and without cognitive dementia.MethodsSequencing all the coding exons of ANXA11 and intron-exon boundaries in 18 familial amyotrophic lateral sclerosis (FALS), 353 unrelated sporadic amyotrophic lateral sclerosis (SALS), and 12 Chinese patients with ALS-frontotemporal lobar dementia (ALS-FTD). The transcripts in peripheral blood generated from a splicing mutation were examined by reverse transcriptase PCR.ResultsWe identified 6 nonsynonymous heterozygous mutations (5 novel and 1 recurrent), 1 splice site mutation, and 1 deletion of 10 amino acids (not accounted in the mutant frequency) in 11 unrelated patients, accounting for a mutant frequency of 5.6% (1/18) in FALS, 2.3% (8/353) in SALS, and 8.3% (1/12) in ALS-FTD. The deletion of 10 amino acids was detected in 1 clinically undetermined male with an ALS family history who had atrophy in hand muscles and myotonic discharges revealed by EMG. The novel p. P36R mutation was identified in 1 FALS index, 1 patient with SALS, and 1 ALS-FTD. The splicing mutation (c.174-2A>G) caused in-frame skipping of the entire exon 6. The rest missense mutations including p.D40G, p.V128M, p.S229R, p.R302C and p.G491R were found in 6 unrelated patients with SALS.ConclusionsThe ANXA11 gene is one of the most frequently mutated genes in Chinese patients with SALS. A canonical splice site mutation leading to skipping of the entire exon 6 further supports the loss-of-function mechanism. In addition, the study findings further expand the ANXA11 phenotype, first highlighting its pathogenic role in ALS-FTD.

S55. ANXA11 mutations prevail in Chinese ALS patients with and without cognitive dementia

Introduction Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by progressive paralysis and ultimately respiratory failure within 5 years of symptom onset. Approximately 5–10% of ALS cases exhibit familial inheritance (FALS) and causative gene mutations can be found in 60% of FALS patients. The remaining 90–95% of ALS cases show sporadic manner (SALS) and mutations in the same genes are responsible for 10% of SALS patients. To date, rare variants in more than 30 genes have been reported to cause or be associated with ALS. Recently, Smith and et al. identified mutations in ANXA11 in ALS patients of European ancestry but pathogenicity of ANXA11 in other ALS cohorts remained unproved. In the current study, we investigated ANXA11 mutations in Chinese ALS patients with or without cognitive decline. Methods: Study population A total of 383 Chinese ALS patients were recruited at ALS clinic of Neurology Department, Peking Union Medical College Hospital (PUMCH) from January 2016 to August 2017. Mutation screening All coding exons and at least 100 bp of flanking introns of ANXA11(NM_145869) were sequenced using ABI 3730 automated DNA-sequencing system. Rare variants (MAF Transcripts investigation of the splicing mutation Total RNA was extracted using TRIzol (Invitrogen) from peripheral white blood cells. Then 2.5 μ g RNA were used to perform Reverse transcriptase-PCR. cDNA was amplified using primer pair ANXA11-RT-F(5′-CCATGAGCTACCCTGGCTAT-3′) and ANXA11-RT-R(5′-GACTCCCCAGGCAGTCAAT-3′) locating at ANXA11 exon 4 and exon 8 (shown in Fig. 3), respectively. The PCR products were isolated on a 1.5% agarose gel. DNA fragments of interest were gel-purified and sequenced. Results We identified 6 nonsynonymous heterozygous mutations (c.107C>G, p.P36R; c.119A>G, p.D40G; c.382G>A, p.V128M; c.687T>A, p.S229R; c.904C>T, p.R302C; c.1471G>A, p.G491R) and 1 splice-site mutation(c.174-2A>G, p.A58_Q187del) in 10 unrelated patients, accounting for a mutant frequency of 5.6% (1/18) in FALS, 2.3% (8/353) in SALS and 8.3% (1/12) in ALS-FTD. A novel p. P36R mutation was identified in one FALS index, one SALS patient and one ALS-FTD. The splicing mutation(c.174-2A>G) caused in-frame skipping of the entire exon 6 and further supported the loss-of-function mechanism. Conclusion ANXA11 gene is the most frequently mutated genes in Chinese patients with SALS. The study findings further expand the ANXA11 phenotype, firstly highlighting its pathogenic role in ALS-FTD.

F45. Genetic analysis of TIA1 gene in Chinese patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive lethal neurodegenerative disorder characterized by affecting the upper and lower motor neurons of the brain, brainstem and spinal cord. Approximately 15% of ALS patients also suffering from frontotemporal dementia (FTD). Very recently, six missense mutations affecting the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1) were identified in 1039 non-Hispanic white ALS and ALS-FTD patients. Mutations in the TIA1 gene were suggest to account for ∼2% FALS and <0.5% sporadic ALS (SALS). Those data suggest that TIA1 mutations might be a rare cause of ALS ± FTD. Studies analyzing Asian ALS patient cohorts have not been reported. Previous studies have shown that mutations in the ALS causal genes varied among ethnic populations, such as the G4C2 repeat expansion in the C9orf72 gene is rare in Asian people. To investigate the frequency and spectrum of TIA1 mutations further, we firstly performed mutational screening of TIA1 in a large cohort of ALS/ALS-FTD patients of Chinese origin. The study included 576 Chinese ALS/ALS-FTD patients (FALS = 28; SALS = 535; ALS-FTD = 13) and 500 neurologically normal control subjects. All participants were of Han descent and from mainland China. ALS/ALS-FTD patients were registered at ALS clinic of Neurology Department, Peking Union Medical College Hospital from January 2016 to August 2017. TIA1 (NM_022173) exons 11, 12 and 13 encoding the prion-like LCD domain of TIA1 were sequenced in all 576 cases. Resulting chromatograms were aligned to reference human genome ( UCSC hg19) using CodonCode Aligner tool. All patients harboring mutations of the TIA1 were examined other common ALS causal genes including SOD1, ANXA11, FUS, OPTN, UBQLN2, TARDB and C9orf72. Besides, the identified mutations were subsequently screened in 500 controls. TIA1 sequence analysis revealed a novel heterozygous missense mutation, c.973A>G (p.N325D), in a sporadic ALS case. The variant was not present in our 500 neurologically normal controls as well as several public data bases includingExAC, gnomAD, 1000 Genomes Project and SNP150. The p.N325D substitution affects an highly conserved amino acid in the prion-like LCD domain. Moreover, Four distinct programs – PolyPhen2, Mutation Taster, SIFT and CADD – all predicted p.N325D as a damaging mutation. In conclusion, we have identified a novel mutation in the TIA1 gene in SALS patients of Chinese origin. Our findings provide an overview of the TIA1 mutation in Chinese ALS patients. We propose that the TIA1 mutation is not a frequent mutation in Chinese ALS patients.

F47. Screening of GLE1 mutations in Chinese amyotrophic lateral sclerosis patients

Introduction Amyotrophic lateral sclerosis (ALS) is a fatal disease involving both upper and lower motor neuron, resulting in a 3–5 year of survival from symptom onset caused by rapidly progressive paralysis and respiratory failure. It is etiologically heterogeneous. Approximately 90% of ALS cases are sporadic (SALS) with unknown causes. But The remaining 10% of patients have a family history (FALS) and harbor a causative gene mutation, reflecting genetic factor play an important role in the pathogenesis of ALS. To date, mutations in over 20 genes have been reported in ALS populations. Mutations in GLE1 are the causation of two fetal motoneuron diseases: lethal congenital contracture syndrome 1 (LCCS1) and lethal arthrogryposis with anterior horn cell disease (LAAHD). Recently, Kaneb et al. identifiedGLE1variants within sporadic and familial Caucasian ALS cases, supporting defects in RNA metabolism were associated with pathogenesis of ALS. However, GLE1 mutations have not been investigated in Chinese ALS patients so far. Accordingly, we evaluated whether GLE1 mutations harbored in ALS patients from mainland China. Methods The current study recruited probands of 20 ALS families (mean age of onset was 50.1 ± 10.9 years; 10 females, 10 males), 230 SALS patients (mean age of onset was 52.1 ± 11.9 years; 96 females, 134 males). All 16 exons (plus 50 bp of flanking introns) of GLE1 (NM_001003722.1) including the entire coding region were amplified using polymerase chain reaction (PCR). The reaction conditions of PCR were as follows: 5 min of denaturation at 95 °C, 8 cycles were used with 20 s at 94 °C, 20 s at 65 °C (decreasing by 1 °C with each cycle) and 30 s at 72 °C. 20 s at 94 °C, 20 s at 58 °C and 30 s at 72 °C for the subsequent 34 cycles, a final extension step at 72 °C for 5 min. PCR products were subjected to Sanger sequencing using ABI 3730 automated DNA-sequencing system (Applied Biosystems). The sequences were aligned with reference sequence using CodonCode Aligner. Results GLE1 mutation screening of 250 ALS cases revealed 4 synonymous genetic variants(c.444G > A, p. R148R; c.946C > A, p. R316R; c.1641T > C, p. Y547Y; c.2082C > T, P. S694S), which presented in dbSNP database. Bioinformatic analysis using ESE finder and Human Splicing Finder 3.0 showed that all the silent mutations did not affect transcription process. We did not identify any novel or reported rare variants in all 16 coding exons of GLE1from 250 Chinese ALS patients. Conclusion In summary, our results suggested that GLE1 mutations are not common in FALS and SALS of Chinese origin. Further study in larger and additional populations would be required to evaluate the role of GLE1 in ALS causation.

ANXA11 mutations prevail in Chinese amyotrophic lateral sclerosis patients with and without cognitive dementia (P1.320)

ANXA11 mutations prevail in Chinese amyotrophic lateral sclerosis patients with and without cognitive dementia (P1.320)

Screening for possible oligogenic pathogenesis in Chinese sporadic ALS patients

We investigated all coding regions of 17 known amyotrophic lateral sclerosis (ALS)-related genes in 311 sporadic ALS patients who were of Chinese ancestry using next-generation sequencing technology. All nonsynonymous variants identified were confirmed by Sanger sequencing. 29 (9.32%) patients harbored at least one pathogenic or likely pathogenic variants. Nine (2.8%) patients harbored two or three variants which frequency <1% in population databases that may be related to oligogenic pathogenesis. A higher allele frequency was observed in East Asian than in European patients for the majority variants identified in this screening, which may indicate that genetic factors are responsible for the different clinical characteristics between Chinese and European ALS patients. Our study reports the results of extensive genetic screening and is the first to investigate the possible oligogenic pathogenesis in Chinese sporadic ALS patients. These findings are useful for exploring ALS pathogenesis and treatment strategies.

Phenotypic differences of amyotrophic lateral sclerosis (ALS) in China and Germany

The aim of this study is to explore phenotypical differences of amyotrophic lateral sclerosis (ALS) between two cohorts from Germany and China. Registry-based studies of ALS were conducted in South-West Germany from 2010 to 2014 and an ALS clinic in Beijing from 2013 to 2016, respectively. Demographic and clinical features of 663 German and 276 Chinese ALS patients were collected and compared. Mean age-at-onset was higher in German than in Chinese ALS patients [66.6years (95% CI 65.7, 67.5) vs. 53.2years (95% CI 52.0, 54.5)]. Age distribution of ALS patients peaked around 70-74years in Germany and 50-54years in China. Bulbar onset was more prevalent among German than among Chinese patients (35.9 vs. 22.8%). Diagnostic delay was higher in the Chinese than in the German study sample (12 vs. 5months). Cognitive deficits were more pronounced in the Chinese cohort. Both cohorts differed in smoking habits, prevalence of diabetes and in body mass index (BMI). The apparent discrepancies between German and Chinese ALS patients (age at onset, gender distribution, bulbar forms, cognitive dysfunction, risk factors) reveal a quite different clinical phenotype in China, maybe due to socioeconomic status, environmental factors or genetic background. The observed differences in phenotype need to be pursued by further epidemiological studies on environmental and genetic risk factors.

Screening of GLE1 mutations in Chinese amyotrophic lateral sclerosis patients

Amyotrophic lateral sclerosis (ALS) is a lethal neurological disease primarily involving the spinal cord, brainstem, and corticospinal tract. Recently, mutations in the GLE1 gene were reported in Caucasian ALS patients. To inquire whether Chinese ALS patients carried causal mutations in the gene, we screened all 16 coding exons of GLE1 with Sanger sequencing in a Han Chinese cohort of 250 ALS cases. No nonsynonymous coding variants were detected. Our results suggest that pathogenic variants in the GLE1 gene are rare in Chinese ALS patients.

The clinical picture and demographics of ALS in China

Amyotrophic lateral sclerosis (ALS) is the neurodegenerative disease involving both upper motor neurons and lower motor neurons. According to a multicentre study from Chinese ALS association, the mean age at onset of ALS is 52.4±12.1 years in China,which is earlier than many developed countries. ALS is more common in clinical practice than before, the incidence seems increasing in the past years, although there is still no exact data of epidemiology study based on population in China. Population based case-control investigations of genetic and environmental factor are needed to identify the potential factors for Chinese ALS patients.