Amyotrophic lateral sclerosis & frontotemporal degeneration最新文献

{"title":"Slowly progressing Amyotrophic lateral sclerosis associated with the F21L variant in the SOD1 gene: Demographic and clinical characteristics.","authors":"Cristian Correa-Arrieta, Sandra Castellar-Leones, John Jairo Forero Diaz, Martha Peña-Preciado, Fernando Ortiz-Corredor","doi":"10.1080/21678421.2024.2416669","DOIUrl":"https://doi.org/10.1080/21678421.2024.2416669","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which genetic variants can significantly influence clinical presentation and prognosis. This study aims to describe the demographic and clinical characteristics of ALS patients carrying the SOD1: c.63C > G (p.Phe21Leu) [NM_000454.4] variant, as treated at a national reference center in Colombia.</p><p><strong>Methods: </strong>A descriptive study was conducted on patients identified with the SOD1: c.63C > G (p.Phe21Leu) [NM_000454.4] variant, selected from the database of a neuromuscular disease center in Colombia. Demographic and clinical data were collected through medical records and patient interviews. Molecular analysis was performed using PCR and automated sequencing to confirm the presence of the variant.</p><p><strong>Results: </strong>Eleven patients with SOD1: c.63C > G (p.Phe21Leu) [NM_000454.4] variant were identified. The mean age at onset was 48.4 years, with a mean disease duration of 76.7 months. The majority (90.9%) exhibited a slowly progressive course, predominantly with spinal onset and no cognitive impairment. Bulbar symptoms developed in 72.2% of the patients, and 81.8% required noninvasive ventilation. A family history of ALS or other neurodegenerative disorders was present in 54.5% of the patients.</p><p><strong>Conclusions: </strong>The SOD1: c.63C > G (p.Phe21Leu) [NM_000454.4] variant is associated with a slowly progressive ALS phenotype, characterized by predominant lower motor neuron involvement and delayed onset of bulbar and respiratory symptoms. This variant appears to be predominantly distributed in central Colombia. Early detection of this variant may enable timely interventions and personalized care plans. Further research is required to establish a definitive causal relationship between this variant and the observed clinical course.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurologists' understanding of reproductive medicine options for genetic forms of motor neuron disease.","authors":"Shanice Allen, Jade Howard, Christopher J Mcdermott, Felicity Boardman, Alisdair Mcneill","doi":"10.1080/21678421.2024.2416677","DOIUrl":"10.1080/21678421.2024.2416677","url":null,"abstract":"<p><strong>Objectives: </strong>To examine the knowledge, confidence and practice of motor neuron disease (MND) clinicians toward discussing reproductive options with people who carry a causal variant in an MND gene (both clinically affected and asymptomatic).</p><p><strong>Methods: </strong>An online cross-sectional survey was distributed nationwide to UK MND clinicians and clinical geneticists and genetic counselors. The survey assessed respondents' understanding on reproductive medicine techniques; their confidence in discussing reproductive medicine options and their access to information resources.</p><p><strong>Results: </strong>Seventy six clinicians responded to the online survey (45 neurology clinicians and 31 clinical geneticists). MND clinicians had limited knowledge and low confidence in discussing reproductive medicine options. Geneticists were more likely to carry out reproductive genetic counseling with very few MND clinicians reporting undertaking these discussions. Further, 57% of the 45 MND clinicians surveyed reported to have never made a referral for reproductive genetic counseling. Multiple barriers to offering reproductive counseling or referral were identified including a lack of knowledge, lack of awareness of the different options, lack of clinic time and uncertainty around issues such as funding for PGT and whose responsibility it comes under.</p><p><strong>Conclusions: </strong>There is a need for training and education on reproductive options and referral for these options needs to be integrated within the health system. Developing more resources for both clinicians and patients is required as MND clinicians reported a lack of resources.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spanish adaptation of the Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS).","authors":"Javier Mascías Cadavid, Ratko Radakovic, Chelsea Radakovic, Yolanda Moran Benito, Saúl Marín Esteban, Francisco Rodríguez-Santos, Teresa Salas Campos","doi":"10.1080/21678421.2024.2416665","DOIUrl":"https://doi.org/10.1080/21678421.2024.2416665","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is characterized functional decline, traditionally measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). The Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) is an alternative comprehensive, detailed functional disability measure for people with ALS (pwALS), not yet translated to Spanish. The aim of this study was to translate and validate the Spanish ROADS. 53 Spanish speaking pwALS were recruited. They completed the ALSFRS-R and Spanish ROADS. Reliability (internal consistency, intra-class correlation) and validity (ALSFRS-R total and item-total correlations) were determined. The Spanish ROADS internal consistency reliability was excellent (Cronbach's standardized alpha = 0.94), the test-retest reliability intra-class correlation value was 0.93. There was a strong significant correlation between the Spanish ROADS and ALSFRS-R totals (r_s(52) = .89, <i>p</i> < .001). Additionally, the ALSFRS-R subscales and ROADS items correlations showed domain-to-item specific expected significant correlations. The Spanish ROADS is a psychometrically robust, valid and reliable measure for quantifying functional disability for pwALS.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What do you think caused your ALS? An analysis of the CDC national amyotrophic lateral sclerosis patient registry qualitative risk factor data using artificial intelligence and qualitative methodology.","authors":"Danielle Boyce, Jaime Raymond, Theodore C Larson, Eddie Kirkland, D Kevin Horton, Paul Mehta","doi":"10.1080/21678421.2024.2349920","DOIUrl":"10.1080/21678421.2024.2349920","url":null,"abstract":"<p><strong>Objective: </strong>Amyotrophic lateral sclerosis (ALS) is an incurable, progressive neurodegenerative disease with a significant health burden and poorly understood etiology. This analysis assessed the narrative responses from 3,061 participants in the Centers for Disease Control and Prevention's National ALS Registry who answered the question, \"What do you think caused your ALS?\"</p><p><strong>Methods: </strong>Data analysis used qualitative methods and artificial intelligence (AI) using natural language processing (NLP), specifically, Bidirectional Encoder Representations from Transformers (BERT) to explore responses regarding participants' perceptions of the cause of their disease.</p><p><strong>Results: </strong>Both qualitative and AI analysis methods revealed several, often aligned themes, which pointed to perceived causes including genetic, environmental, and military exposures. However, the qualitative analysis revealed detailed themes and subthemes, providing a more comprehensive understanding of participants' perceptions. Although there were areas of alignment between AI and qualitative analysis, AI's broader categories did not capture the nuances discovered using the more traditional, qualitative approach. The qualitative analysis also revealed that the potential causes of ALS were described within narratives that sometimes indicate self-blame and other maladaptive coping mechanisms.</p><p><strong>Conclusions: </strong>This analysis highlights the diverse range of factors that individuals with ALS consider as perceived causes for their disease. Understanding these perceptions can help clinicians to better support people living with ALS (PLWALS). The analysis highlights the benefits of using traditional qualitative methods to supplement or improve upon AI-based approaches. This rapidly evolving area of data science has the potential to remove barriers to accessing the rich narratives of people with lived experience.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"615-624"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/21678421.2024.2326288","DOIUrl":"10.1080/21678421.2024.2326288","url":null,"abstract":"","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"I"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotype-phenotype association and functional analysis of <i>hnRNPA1</i> mutations in amyotrophic lateral sclerosis.","authors":"Xinyi Zhang, Ye Sun, Xinzhe Zhang, Dongchao Shen, Shi Shu, Xunzhe Yang, Mingsheng Liu, Liying Cui, Qing Liu, Xue Zhang","doi":"10.1080/21678421.2024.2346502","DOIUrl":"10.1080/21678421.2024.2346502","url":null,"abstract":"<p><strong>Background: </strong>Pathogenic variants in <i>hnRNPA1</i> have been reported in amyotrophic lateral sclerosis (ALS) patients. However, studies on <i>hnRNPA1</i> mutant spectrum and pathogenicity of variants were rare.</p><p><strong>Methods: </strong>We performed whole exome sequencing of ALS-associated genes and subsequent verification of rare variants in <i>hnRNPA1</i> in our ALS patients. The <i>hnRNPA1</i> mutations reported in literature were reviewed and combined with our results to determine the genotype-phenotype relationship. Functional analysis of the novel variant p.G195A was performed in vitro by transfection of mutant <i>hnRNPA1</i> into 293T cell.</p><p><strong>Results: </strong>Among 207 ALS patients recruited, 3 rare <i>hnRNPA1</i> variants were identified (mutant frequency 1.45%), including two recurrent mutations (p.P340S and p.G283R), and a novel rare variant p.G195A. In combination with previous reports, there are 27 ALS patients with 15 <i>hnRNPA1</i> mutations identified. Disease onset age was 47.90 ± 1.52 years with predominant limb onset. The p.P340S mutation caused flail arm syndrome (FAS) in two independent families with extended life expectancy. The newly identified p.G195A mutation, lying at the start of the PrLD (\"prion-like\" domain)/LCD (low-complexity domain), causes local structural changes in 3D protein prediction. Upon sodium arsenite exposure, mutant hnRNPA1 retained in the nucleus but deficit of cytoplasmic G3BP1-positive stress granule clearance was observed. This is different from the p.P340S mutation which caused both cytoplasmic translocation and stress granule formation. No cytoplasmic TDP-43 translocation was observed.</p><p><strong>Conclusion: </strong>Mutations in <i>hnRNPA1</i> are overall minor in ALS patients. The p.P340S mutation is associated with manifestation of FAS. Mutations in LCD of <i>hnRNPA1</i> cause stress granule misprocessing.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"600-607"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Residential exposure associations with ALS risk, survival, and phenotype: a Michigan-based case-control study.","authors":"Stephen A Goutman, Jonathan Boss, Dae Gyu Jang, Caroline Piecuch, Hasan Farid, Madeleine Batra, Bhramar Mukherjee, Eva L Feldman, Stuart A Batterman","doi":"10.1080/21678421.2024.2336110","DOIUrl":"10.1080/21678421.2024.2336110","url":null,"abstract":"<p><strong>Background: </strong>Environmental exposures impact amyotrophic lateral sclerosis (ALS) risk and progression, a fatal and progressive neurodegenerative disease. Better characterization of these exposures is needed to decrease disease burden.</p><p><strong>Objective: </strong>To identify exposures in the residential setting that associate with ALS risk, survival, and onset segment.</p><p><strong>Methods: </strong>ALS and control participants recruited from University of Michigan completed a survey that ascertained exposure risks in the residential setting. ALS risk was assessed using logistic regression models followed by latent profile analysis to consider exposure profiles. A case-only analysis considered the contribution of the residential exposure variables via a Cox proportional hazards model for survival outcomes and multinomial logistic regression for onset segment, a polytomous outcome.</p><p><strong>Results: </strong>This study included 367 ALS and 255 control participants. Twelve residential variables were associated with ALS risk after correcting for multiple comparison testing, with storage in an attached garage of chemical products including gasoline or kerosene (odds ratio (OR) = 1.14, <i>p</i>_adjusted < 0.001), gasoline-powered equipment (OR = 1.16, <i>p</i>_adjusted < 0.001), and lawn care products (OR = 1.15, <i>p</i>_adjusted < 0.001) representing the top three risk factors sorted by <i>p</i>_adjusted. Latent profile analysis indicated that storage of these chemical products in both attached and detached garages increased ALS risk. Although residential variables were not associated with poorer ALS survival following multiple testing corrections, storing pesticides, lawn care products, and woodworking supplies in the home were associated with shorter ALS survival using nominal <i>p</i> values. No exposures were associated with ALS onset segment.</p><p><strong>Conclusion: </strong>Residential exposures may be important modifiable components of the ALS susceptibility and prognosis exposome.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"543-553"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of amyotrophic lateral sclerosis before and during the COVID-19 pandemic: evidence from an 8-year population-based study in Central Italy based on healthcare utilization databases.","authors":"Federico Maria Sopranzi, Andrea Faragalli, Marco Pompili, Flavia Carle, Rosaria Gesuita, Maria Gabriella Ceravolo","doi":"10.1080/21678421.2024.2336127","DOIUrl":"10.1080/21678421.2024.2336127","url":null,"abstract":"<p><strong>Background: </strong>Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder with a high multidimensional burden, with an obscure etiopathogenesis.</p><p><strong>Methods: </strong>We designed a longitudinal, population-based study of people residing in Central Italy (Marche Region) who were beneficiaries of the National Health System. People with an unprecedented ALS hospitalization (335.20 ICD-9 CM) or tagged with an ALS exemption between 2014 and 2021 were considered incident cases. ALS cases residing in the region for <3 years or with an active ALS exemption or hospitalized for ALS before 2014 were excluded. We used secondary sources to identify new ALS diagnoses. The regional referral center for ALS's database was used to test the accuracy of secondary sources in detecting cases. ALS mean incidence was compared to that reported in similar studies conducted in Italy. The incidence rate trend adjusted by sex and age was evaluated using the Poisson regression model.</p><p><strong>Results: </strong>We detected 425 new ALS cases (median age: 70y) in the 2014-2021 period, with a mean incidence of 3.5:100,000 py (95%CI: 3.2-3.8; M:F = 1.2), similar to that reported in similar studies conducted in Italy. No trend was observed during 2014-2019. After including 2020-2021 in the model, we observed a mean decrease in incidence of 5.8% (95% CI 2.0%; 9.5%, p = 0.003).</p><p><strong>Conclusion: </strong>We show a decrease in the incidence rate of ALS in Marche, during the 2014-2021 period, as a possible outcome of a delayed neurological assessment and diagnosis during the pandemic. An ad hoc developed identification algorithm, based on healthcare utilization databases, is a valuable tool to assess the health impact of global contingencies.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"554-562"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dyspnea (breathlessness) in amyotrophic lateral sclerosis/motor neuron disease: prevalence, progression, severity, and correlates.","authors":"Carolyn A Young, Amina Chaouch, Christopher J Mcdermott, Ammar Al-Chalabi, Suresh K Chhetri, Kevin Talbot, Timothy Harrower, Richard W Orrell, Joe Annadale, C Oliver Hanemann, Antonio Scalfari, Alan Tennant, Roger Mills","doi":"10.1080/21678421.2024.2322545","DOIUrl":"10.1080/21678421.2024.2322545","url":null,"abstract":"<p><strong>Objective: </strong>Dyspnea, or breathlessness, is an important symptom in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). We examined the measurement properties of the Dyspnea-12.</p><p><strong>Methods: </strong>Rasch analysis enabled conversion of raw Dyspnea-12 scores to interval level metric equivalents. Converted data were used to perform trajectory modeling; those following different trajectories were compared for demographic, clinical, symptom, and functioning characteristics. Logistic regression examined differences between distinct trajectories.</p><p><strong>Results: </strong>In 1022 people, at baseline, mean metric Dyspnea-12 was 7.6 (SD 9.3). 49.8% had dyspnea, severe in 12.6%. Trajectory analysis over 28 months revealed three breathlessness trajectories: group 1 reported none at baseline/follow-up (42.7%); group 2 significantly increased over time (9.4%); group 3 had a much higher level at baseline which rose over follow-up (47.9%). Group 3 had worse outcomes on all symptoms, functioning and quality of life; compared to group 1, their odds of: respiratory onset sixfold greater; King's stage ≥3 2.9 greater; increased odds of being bothered by choking, head drop, fasciculations, and muscle cramps; fatigue and anxiety also elevated (<i>p</i> < .01).</p><p><strong>Conclusion: </strong>Dyspnea is a cardinal symptom in ALS/MND and can be quickly measured using the Dyspnea-12. Raw scores can easily be converted to interval level measurement, for valid change scores and trajectory modeling. Dyspnea trajectories reveal different patterns, showing that clinical services must provide monitoring which is customized to individual patient need. Almost half of this large population had worsening dyspnea, confirming the importance of respiratory monitoring and interventions being integrated into routine ALS care.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"475-485"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and <i>in silico</i> analysis of Indian sporadic young onset patient with amyotrophic lateral sclerosis.","authors":"Saileyee Roychowdhury, Deepika Joshi, Vinay Kumar Singh, Mohammed Faruq, Parimal Das","doi":"10.1080/21678421.2024.2324896","DOIUrl":"10.1080/21678421.2024.2324896","url":null,"abstract":"<p><strong>Background: </strong>Amyotrophic lateral sclerosis (ALS) is an old onset devastating neurodegenerative disorder. Young-onset ALS cases especially sporadic ones who are between 25 and 45 years are rarely affected by the disease. Despite the identification of numerous candidate genes associated with ALS, the etiology of the disease remains elusive due to extreme genetic and phenotypic variability. The advent of affordable whole exome sequencing (WES) has opened new avenues for unraveling the disease's pathophysiology better.</p><p><strong>Methods and results: </strong>We aimed to determine the genetic basis of an Indian-origin, young onset sporadic ALS patient with very rapid deterioration of the disease course without any cognitive decline who was screened for mutations in major ALS candidate genes by WES. Variants detected were reconfirmed by Sanger sequencing. The clinicopathological features were investigated and two heterozygous missense variants were identified: R452W, not previously associated with ALS, present in one of the four conserved C terminal domains in <i>ANXA11 and</i> R208W in <i>SIGMAR1</i>, respectively. Both of these variants were predicted to be damaging by pathogenicity prediction tools and various <i>in silico</i> methods.</p><p><strong>Conclusion: </strong>Our study revealed two potentially pathogenic variants in two ALS candidate genes. The genetic makeup of ALS patients from India has been the subject of a few prior studies, but none of them examined <i>ANXA11</i> and <i>SIGMAR1</i> genes so far. These results establish the framework for additional research into the pathogenic processes behind these variations that result in sporadic ALS disease and further our understanding of the genetic makeup of Indian ALS patients.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"589-599"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140051230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}