Genetic Spectrum and Variability in Chinese Patients with Amyotrophic Lateral Sclerosis

Liu, Zhijun; Lin, Hui‐Xia; Wei, Qiao; Zhang, Qijie; Chen, Congxin; Tao, Qing‐Qing; Liu, Gong‐Lu; Wang, Ni; Gitler, Aaron D.; Li, Hongfu; Wu, Zhi‐Ying

doi:10.14336/ad.2019.0215

Cited by 48 publications

(41 citation statements)

References 33 publications

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“…The majority of ALS cases are sporadic without apparent family history of the disease, whereas only 5–10% of cases are familial with high genetic heterogeneity. More than 30 genes have been identified in ALS, and among them, the C9orf72 , SOD1 , FUS , and TDP‐43 are the most common disease‐determining genes 3–4 . Present evidence supports the belief that the development of ALS could be largely attributed to an adverse interplay between genetic and environmental factors, and the disturbances of RNA metabolism, protein degradation, and energy metabolism are the main cellular abnormalities 5 …”

Section: Introductionsupporting

confidence: 62%

“…More than 30 genes have been identified in ALS, and among them, the C9orf72, SOD1, FUS, and TDP-43 are the most common disease-determining genes. [3][4] Present evidence supports the belief that the development of ALS could be largely attributed to an adverse interplay between genetic and environmental factors, and the disturbances of RNA metabolism, protein degradation, and energy metabolism are the main cellular abnormalities. 5 Currently, there are no reliable and sensitive biomarkers for ALS.…”

Section: Introductionmentioning

confidence: 57%

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Promoting identification of amyotrophic lateral sclerosis based on label‐free plasma spectroscopy

Zhang

Chen

Zou

et al. 2020

Ann Clin Transl Neurol

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Objective: Amyotrophic lateral sclerosis (ALS) is an adult-onset fatal neurodegenerative disease which lacks identified biological markers. A label-free plasma surface-enhanced Raman spectroscopy (SERS) method was developed to explore a simple and noninvasive test for ALS. Methods: ALS patients were enrolled serially and plasma samples were collected at the time of diagnosis prior to the start of ALS treatment. SERS spectra were recorded using a Renishaw micro-Raman system. Results: To exclude the interference by varying disease severity, we enrolled three groups of ALS patients, including ALS-1 (n = 60; ALSFRS-R ≥ 42 and time interval ≤ 12 months), ALS-2 (n = 61; ALSFRS-R < 42 and time interval ≤ 12 months), and ALS-3 (n = 61; ALSFRS-R ≥ 38 and time interval> 12 months). The SERS spectra were analyzed using principal component analysis (PCA), which showed that ALS-1, ALS-2, ALS-3, and control groups were separated significantly. Then, decision tree (DT) models and receiver operating characteristic curves were employed and identified that bands at 722 and 739 cm À1 , and ratios of 635-722 cm À1 and 635-739 cm À1 were able to distinguish ALS from controls significantly. Finally, we highlighted six metabolism pathways correlated with ALS, including phenylalanine-tyrosine-tryptophan biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine metabolism, pantothenate and CoA biosynthesis, porphyrin and chlorophyll metabolism, and pyrimidine metabolism. Interpretation: Plasma SERS could be a promising tool for the detection of ALS. The bands at 722 and 739 cm À1 , and the ratios of 635-722 cm À1 and 635-739 cm À1 could serve as potential indicator for ALS.

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Section: Introductionsupporting

confidence: 62%

Section: Introductionmentioning

confidence: 57%

Promoting identification of amyotrophic lateral sclerosis based on label‐free plasma spectroscopy

Zhang

Chen

Zou

et al. 2020

Ann Clin Transl Neurol

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“…For age of onset, motor neuron impairments, disease duration, and FTD, the weighted mean ± SD, and weighted percentages are given, taking into account the numbers of patients studied. Data for each gene were collected from the following reference studies, then summarized: hnRNPA1: [ 168 ]; SETX: [ 169 , 170 , 171 , 172 , 173 ]; SOD1: [ 24 , 92 , 160 , 161 , 171 , 172 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 ]; TBK1: [ 189 , 190 , 191 , 192 ]; FUS: [ 24 , 92 , 145 , 146 , 148 , 170 , 171 , 172 , 179 , 180 , 187 , 188 , 193 , 194 , 195 , 196 ]; OPTN: [ 171 , 180 , 187 , 197 , 198 , 199 ,…”

Section: Figurementioning

confidence: 99%

A Systematic Review of Genotype–Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS

Connolly

Gall

McCluskey

et al. 2020

JPM

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Amyotrophic lateral sclerosis is a rare and fatal neurodegenerative disease characterised by progressive deterioration of upper and lower motor neurons that eventually culminates in severe muscle atrophy, respiratory failure and death. There is a concerning lack of understanding regarding the mechanisms that lead to the onset of ALS and as a result there are no reliable biomarkers that aid in the early detection of the disease nor is there an effective treatment. This review first considers the clinical phenotypes associated with ALS, and discusses the broad categorisation of ALS and ALS-mimic diseases into upper and lower motor neuron diseases, before focusing on the genetic aetiology of ALS and considering the potential relationship of mutations of different genes to variations in phenotype. For this purpose, a systematic review is conducted collating data from 107 original published clinical studies on monogenic forms of the disease, surveying the age and site of onset, disease duration and motor neuron involvement. The collected data highlight the complexity of the disease’s genotype–phenotype relationship, and thus the need for a nuanced approach to the development of clinical assays and therapeutics.

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“…Deep sequencing was performed using Illumina Hiseq2000 system (GrandOmics Biosciences Co, China). Sequencing analysis were performed as we described previously [5]. In order to screen for large deletions or duplications of Dopa-responsive dystonia (DRD) associated genes (GCH1, TH, and SGCE), the Multiplex ligation-dependent probe amplification assay (MLPA) analysis were performed by reference to the method previously reported [6].…”

Section: Targeted Exome-sequencingmentioning

confidence: 99%

Two novel heterozygote mutations of ATM in a Chinese family with dystonia-dominant ataxia telangiectasia and literatures review

Liu¹,

Wang²,

Xu³

2020

Preprint

Self Cite

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Background Ataxia-telangiectasia (A-T) is an autosomal recessive disorder with high clinical heterogeneity. A-T may present in complicated variable forms, mainly including classic A-T and milder forms. Contrary to the classic A-T, the milder form does not present the cardinal features of A-T, including ataxia and telangiectasia. A few ATM mutations have been reported in variant A-T cases manifested as isolated dystonia without any signs of classical A-T. To date, more than 400 disease-related ATM mutations have been identified in patients with A-T. Methods A pedigree with A-T and predominant dystonia were collected. Genetic testing of the proband were performed by target exome-sequencing of a panel designed to cover 101 genes associated with movement disorders. The candidate variants were further confirmed by Sanger sequencing.Results Two novel ATM variants (p.I2683T and p.S2860P) with probable pathogenicity were identified in the family. The proband presented obviously isolated segmental dystonia without any signs of ataxia and telangiectasias. We then reviewed previously published literatures of genetically confirmed A-T cases with predominant dystonia and summarized the clinical characteristics of dystonia-dominant A-T. Conclusion This is the first report of A-T patient with predominant dystonia in China. Dystonia may appear as one of the predominant manifestations or initial symptom of A-T. ATM genetic testing should be early considered for those patients with predominant dystonia, despite without accompanying ataxia or telangiectasia.

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Genetic Spectrum and Variability in Chinese Patients with Amyotrophic Lateral Sclerosis

Cited by 48 publications

References 33 publications

Promoting identification of amyotrophic lateral sclerosis based on label‐free plasma spectroscopy

Promoting identification of amyotrophic lateral sclerosis based on label‐free plasma spectroscopy

A Systematic Review of Genotype–Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS

Two novel heterozygote mutations of ATM in a Chinese family with dystonia-dominant ataxia telangiectasia and literatures review

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