Article
Clinical Neurology
Shlomit Ezer, Muhannad Daana, Julien H. Park, Shira Yanovsky-Dagan, Ulrika Nordstrom, Adily Basal, Simon Edvardson, Ann Saada, Markus Otto, Vardiella Meiner, Stefan L. Marklund, Peter Munch Andersen, Tamar Harel
Summary: Pathogenic variants in the SOD1 gene are associated with a severe motor-neurological syndrome in infants, characterized by global developmental delay and movement impairments. This study identified a homozygous loss-of-function variant in the SOD1 gene in an infant with severe neurological symptoms. Further analysis showed that this variant leads to instability and degeneration of the SOD1 protein. The study highlights the importance of specific valine residues in the SOD1 protein and suggests implications for future therapeutic research.
Article
Clinical Neurology
Delia Gagliardi, Paolo Ripellino, Megi Meneri, Roberto Del Bo, Sara Antognozzi, Giacomo Pietro Comi, Claudio Gobbi, Antonia Ratti, Nicola Ticozzi, Vincenzo Silani, Dario Ronchi, Stefania Corti
Summary: In this study, the authors provided a clinical and molecular description of a cohort of SOD1-ALS patients, revealing the heterogeneity in clinical and molecular characteristics of SOD1 mutations. The cohort exhibited variable expressivity, atypical presentations, and different modes of inheritance. With the availability of SOD1-directed antisense oligonucleotide for SOD1-ALS patients, prompt screening for SOD1 mutations in ALS patients is recommended.
FRONTIERS IN NEUROLOGY
(2023)
Article
Medicine, General & Internal
Wen-Chao Liu, Na Liu, Yan Wang, Chen Huang, Yan-Fang Li, Hao Wang, Xiao-Gang Li, Min Deng
Summary: Research shows that motor neurons (MNs) derived from ALS patient-specific iPSC lines can replicate key aspects of ALS pathogenesis, providing insights into the disease's pathophysiological processes. Incremental mutant expressions of SOD1 in MNs may disrupt cellular function, leading to intracellular calcium disturbances and contributing to the onset of the disease.
CHINESE MEDICAL JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Laura Lopez-Pingarron, Henrique Almeida, Marisol Soria-Aznar, Marcos C. C. Reyes-Gonzales, Maria Pilar Terron, Joaquin J. Garcia
Summary: In this review, the etiology and pathophysiological mechanisms involved in ALS were discussed. ALS can be divided into hereditary and sporadic types, and its pathophysiology is characterized by oxidative stress, glutamate excitotoxicity, and neuroinflammation. Further research is needed to improve our understanding of the etiopathogenesis of ALS and enhance patients' prognosis and survival.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Venkatesan Santhanam, Priya Modi, Umesh K. Mishra, Ishrat Jahan, Namakkal G. Ramesh, Shashank Deep
Summary: In this study, the first iminosugar that inhibits superoxide dismutase fibrillation associated with ALS is reported. Novel triazole and tetrazole embedded iminosugars were successfully synthesized, and one of these designed iminosugars was found to inhibit SOD1 fibrillation and break pre-formed fibrils. Docking and MD simulation studies indicated that this compound interacts with the key residue Arg69 of SOD1 through hydrogen bonding.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biology
Achinta Sannigrahi, Sourav Chowdhury, Bidisha Das, Amrita Banerjee, Animesh Halder, Amaresh Kumar, Mohammed Saleem, Athi N. Naganathan, Sanat Karmakar, Krishnananda Chattopadhyay
Summary: Research shows that the stability and aggregation behavior of SOD1 in membrane environment are affected by Zn, not Cu. Two loop regions play a role in membrane attachment of SOD1 and aggregation driven by lipid-induced conformational changes.
Article
Biochemistry & Molecular Biology
Munishikha Kalia, Mattia Miotto, Deborah Ness, Sarah Opie-Martin, Thomas P. Spargo, Lorenzo Di Rienzo, Tommaso Biagini, Francesco Petrizzelli, Ahmad Al Khleifat, Renata Kabiljo, Tommaso Mazza, Giancarlo Ruocco, Edoardo Milanetti, Richard J. B. Dobson, Ammar Al-Chalabi, Alfredo Iacoangeli
Summary: This study investigates the influence of SOD1 gene mutations on the clinical phenotype of ALS. By analyzing structural and dynamic differences as well as clinical data, it was found that patients carrying MBR variants generally have a longer survival time compared to those with WTL variants. The results support the hypothesis of a decoupling between mechanisms of onset and progression of SOD1 ALS.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Neurosciences
Hirofumi Yamashita, Okiru Komine, Noriko Fujimori-Tonou, Koji Yamanaka
Summary: Non-cell autonomous mechanisms play a role in the pathogenesis of ALS, with glial cells being involved, but the specific role of glial cells has not been fully elucidated. Using microarrays, this study examined mRNA expression changes in the spinal cords of mutant SOD1 transgenic mice, revealing that the majority of differentially expressed genes were highly expressed in microglia and involved in immunological reactions. Additionally, disease-associated microglial genes were upregulated, while homeostatic microglial genes were not, and abnormal expression patterns were predicted in astrocytes. This analysis provides valuable insights into the molecular pathologies and cellular crosstalk in the CNS under physiological and pathological conditions in neurodegenerative diseases.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Valentina Rubino, Giuliana La Rosa, Flavia Carriero, Luca Pipicelli, Simona Damiano, Mariarosaria Santillo, Giuseppe Terrazzano, Giuseppina Ruggiero, Paolo Mondola
Summary: Amyotrophic Lateral Sclerosis (ALS) is a progressive motor neurodegenerative disease with unclear pathogenesis involving astrocytes, microglial cells, and ROS.
Article
Multidisciplinary Sciences
Eanna B. Ryan, Jianhua Yan, Nimrod Miller, Sudarshan Dayanidhi, Yongchao C. Ma, Han-Xiang Deng, Teepu Siddique
Summary: Mutations in the CHCHD10 gene have been linked to various degenerative diseases, including ALS. Transgenic mice overexpressing an ALS-linked CHCHD10 mutation showed an abbreviated lifespan and exhibited pathology in the CNS, skeletal muscle, and cardiac tissue. The study provides insights into the pathogenesis of CHCHD10-related disorders, suggesting a contribution of CNS, skeletal muscle, and cardiac pathology to the disease.
Article
Multidisciplinary Sciences
Hong Yien Tan, Yean Kong Yong, Yuan Chao Xue, Huitao Liu, Tomomi Furihata, Esaki Muthu Shankar, Chen Seng Ng
Summary: Neuroinflammation worsens the development of ALS caused by SOD1 mutation. The mitochondrial damage triggered by ALS leads to the release of mtDNA and RNA:DNA hybrids, activating the IRF3- and IFNAR-dependent IFN-I and interferon-stimulating genes, causing high levels of IFN-I and pro-inflammatory response. Inter-neuronal gap junctions amplify the response through cGAS/DDX41-STING signaling. This highlights the role of a common DNA sensing pathway between SOD1 and TDP-43 in ALS progression.
Article
Geriatrics & Gerontology
Simon Witzel, Matias Wagner, Chen Zhao, Katharina Kandler, Elisabeth Graf, Riccardo Berutti, Konrad Oexle, David Brenner, Juliane Winkelmann, Albert C. Ludolph
Summary: Patients with amyotrophic lateral sclerosis (ALS) exhibit significant differences in disease progression and survival. The genetic contribution to the extremes of this spectrum has not been well characterized. By analyzing the genotype-phenotype correlation, our study provides valuable information for genetic counseling, prognosis estimation, and therapeutic decisions.
NEUROBIOLOGY OF AGING
(2022)
Article
Biology
Tae-Gyun Woo, Min-Ho Yoon, So-mi Kang, Soyoung Park, Jung-Hyun Cho, Young Jun Hwang, Jinsook Ahn, Hyewon Jang, Yun-Jeong Shin, Eui-Man Jung, Nam-Chul Ha, Bae-Hoon Kim, Yonghoon Kwon, Bum-Joon Park
Summary: Using ELISA-based screening, a new small molecule PRG-A01 is identified by Woo et al., which can block the misfolding/aggregation of SOD1 or TDP-43 in a human neuroblastoma cell line. Its administration in an ALS mouse model results in significant improvement in muscle strength, motor neuron viability, and mobility, suggesting its potential therapeutic value in ALS.
COMMUNICATIONS BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Pavlina Hemerkova, Martin Valis
Summary: ALS is a neurodegenerative disease that affects motor neurons and currently has no cure. Free oxygen radicals are known to play a role in the pathogenesis of ALS, while antioxidant enzymes like SOD1 are crucial for antioxidant protection.
Article
Biophysics
Brianna Hnath, Nikolay Dokholyan
Summary: Toxic SOD1 trimers, competing with protective fibril formation, have been identified as off-pathway intermediates. Stabilizing the trimeric SOD1 can prevent fibril formation, making it a potential therapeutic approach for ALS.
BIOPHYSICAL JOURNAL
(2022)
Article
Neurosciences
Jianghong Zhang, Meiying Xue, Yue Mei, Zhigang Li, Zeng Ceng, Yuanyuan Li, Yi Zhang, Na Li, Huajing Teng, Zhong Sheng Sun, Yan Wang
PSYCHOPHARMACOLOGY
(2020)
Review
Biochemistry & Molecular Biology
Zhuang Miao, Yan Wang, Zhongsheng Sun
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Huajing Teng, Wenqing Wei, Qinglan Li, Meiying Xue, Xiaohui Shi, Xianfeng Li, Fengbiao Mao, Zhongsheng Sun
NUCLEIC ACIDS RESEARCH
(2020)
Article
Psychiatry
Yi Zhang, Na Li, Chao Li, Ze Zhang, Huajing Teng, Yan Wang, Tingting Zhao, Leisheng Shi, Kun Zhang, Kun Xia, Jinchen Li, Zhongsheng Sun
TRANSLATIONAL PSYCHIATRY
(2020)
Article
Genetics & Heredity
Yi Gu, Bingwu Xiang, Lina Zhu, Xiuwei Ma, Xiang Chen, Tao Cai
BMC MEDICAL GENETICS
(2020)
Article
Dentistry, Oral Surgery & Medicine
Kai Sun, Miao Yu, Iting Yeh, Liutao Zhang, Haochen Liu, Tao Cai, Hailan Feng, Yang Liu, Dong Han
Summary: This study identified novel variants in the PAX9 gene and indicated that paired domain structural impairment and dominant-negative effect may be the underlying mechanisms of PAX9-related non-syndromic oligodontia.
Article
Dentistry, Oral Surgery & Medicine
Jinglei Zheng, Miao Yu, Haochen Liu, Tao Cai, Hailan Feng, Yang Liu, Dong Han
Summary: This study aimed to identify MSX1 gene variants in Chinese families with nonsyndromic oligodontia and analyze their functional effects. Five novel MSX1 variants were found, with preliminary in vitro studies showing abnormal subcellular localization compared to the wild type. Three variants were classified as pathogenic, while two were of uncertain significance. The study expanded the spectrum of nonsyndromic oligodontia variants and provided valuable information for genetic counseling.
INTERNATIONAL JOURNAL OF ORAL SCIENCE
(2021)
Article
Genetics & Heredity
Yuan Li, Jianjun Xiong, Yi Zhang, Lin Xu, Jianyun Liu, Tao Cai
Summary: A cohort study involving 542 individuals in 166 families with congenital hearing loss identified three variants in five affected individuals from two unrelated families. Mutations in ATP6V1B2 and TJP2 were associated with hearing loss, while a novel variant in KIF11 was linked to sensorineural hearing loss and epilepsy. Genotype-phenotype analysis revealed potential genetic mechanisms underlying these disorders.
FRONTIERS IN GENETICS
(2021)
Article
Cell Biology
Xiaoxing Kou, Jin Liu, Dandan Wang, Ming Yu, Can Li, Lu Lu, Chider Chen, Dawei Liu, Wenjing Yu, Tingting Yu, Yao Liu, Xueli Mao, Ali Naji, Tao Cai, Lingyun Sun, Songtao Shi
Summary: Diabetes is a major public health issue with no cure. This study reveals that implantation of pancreas-derived mesenchymal stem cells (PMSCs) can regenerate the exocrine pancreas and provide therapy for diabetes. The mechanism involves the elevation of interleukin-6 (IL-6) in the regenerated pancreas, which inhibits the production of IL-17 and rescues damaged pancreatic cells.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Genetics & Heredity
Tao Cai, Jieting Huang, Xiuwei Ma, Siqi Hu, Lina Zhu, Jinwen Zhu, Zhichun Feng
Summary: In this study, two variants in the ALG13 gene were identified in individuals with intellectual disability and/or development delay. One of the variants may represent a case of X-linked recessive disorder.
FRONTIERS IN GENETICS
(2022)
Article
Endocrinology & Metabolism
Zhuo-Jing Luo, Hongzhuo Li, Liu Yang, Baoling Kang, Tao Cai
Summary: Diagnosis of rare skeletal diseases is primarily based on clinical phenotype and radiographic analysis. However, the genetic causes of these diseases are not well understood. This study identified two genomic mutations associated with multiple epiphyseal dysplasia (MED) through exome sequencing. One mutation was found in the COL2A1 gene and the other in the USP9X gene, suggesting a new clinical entity and shedding light on the role of USP9X in MED-associated disorders.
Article
Biochemistry & Molecular Biology
Yuan Li, Guozhu Ning, Baoling Kang, Jinwen Zhu, Xiao-Yang Wang, Qiang Wang, Tao Cai
Summary: Hereditary hearing loss is a genetically heterogeneous disorder, with over 150 genes identified to be linked to it. A new homozygous missense variant in the OXR1 gene was discovered, and knockdown of the ortholog oxr1b gene in zebrafish resulted in developmental defects in the sensory ganglia of the ear. Mutations in other genes associated with OXR1 were also found to be related to hearing loss.
HUMAN MOLECULAR GENETICS
(2023)
Article
Dentistry, Oral Surgery & Medicine
Jianjun Xiong, Xi Wang, Chunxin Fan, Jizhou Yan, Jinwen Zhu, Tao Cai
Summary: This study identified a novel candidate gene variant in the FRK gene for a patient with HFM and mandibular hypoplasia, and revealed its effects on craniofacial and embryonic development in zebrafish.
Article
Genetics & Heredity
Baoling Kang, Xinshu Lu, Jianjun Xiong, Yuan Li, Jinwen Zhu, Tao Cai
Summary: In this study, four compound heterozygous variants in the CDH23 gene were identified through whole-exome sequencing. These variants may serve as potential genetic causes for hearing loss. The findings significantly expand the mutation spectrum of CDH23-associated hearing loss.
FRONTIERS IN GENETICS
(2022)
Article
Medicine, Research & Experimental
Huajing Teng, Meiying Xue, Jialong Liang, Xingxing Wang, Lu Wang, Wenqing Wei, Chao Li, Ze Zhang, Qinglan Li, Xia Ran, Xiaohui Shi, Wanshi Cai, Weihu Wang, Hengjun Gao, Zhongsheng Sun
Article
Genetics & Heredity
Katerina S. Kucera, Beth Lincoln Boyea, Brooke Migliore, Sarah Nelson Potter, Veronica R. Robles, Oksana Kutsa, Heidi Cope, Katherine C. Okoniewski, Anne Wheeler, Catherine W. Rehder, Edward C. Smith, Holly L. Peay
Summary: Screening for elevated CK-MM levels in dried blood spots is a feasible method to identify newborns with DMD. Including specific cutoffs, repeat testing, and genetic sequencing can improve the accuracy and sensitivity of screening.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Madeline Currey, Ilana Solomon, Sarah Mcgraw, Jenny Shen, Francisco Munoz, Ernesto Sosa, Vanessa Puello-Lozano, Sam Wing, Lisa Lopez, Michelle Afkhami, Janine Lobello, Szabolcs Szelinger, Stacy W. Gray
Summary: This study conducted qualitative interviews with cancer patients and providers to identify gaps in clinical care and propose care delivery solutions for the return of secondary germline findings. The responses of patients varied depending on the amount of pre-test counseling they received, and providers identified insufficient clinic time as a major barrier to pretest education. Online support tools and standardized pre-test education models were favored by providers. There were differing perspectives on how pre-test education should be integrated into clinical workflows, but agreement on the inclusion of differences between somatic and germline testing, likelihood of medically actionable findings, and the possibility of being referred to a genetics provider.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kiely N. James, Shimul Chowdhury, Yan Ding, Sergey Batalov, Kelly Watkins, Yong Hyun Kwon, Lucitia Van Der Kraan, Katarzyna Ellsworth, Stephen F. Kingsmore, Lucia Guidugli
Summary: This study used genome sequencing to detect a wide range of copy-number variants (CNVs) and other non-single nucleotide variant/indel variant types. These genetic alterations accounted for 15.8% of reported variants, with deletions being the most common type. The study also found that additional genetic tests were ordered in some cases, but failed to report the variants detected by genome sequencing.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Asem Berkalieva, Nicole R. Kelly, Ashley Fisher, Samuel F. Hohmann, Monisha Sebastin, Miranda Di Biase, Katherine E. Bonini, Priya Marathe, Jacqueline A. Odgis, Sabrina A. Suckiel, Michelle A. Ramos, Rosamond Rhodes, Noura S. Abul-Husn, John M. Greally, Carol R. Horowitz, Melissa P. Wasserstein, Eimear E. Kenny, Bruce D. Gelb, Bart S. Ferket
Summary: The study aims to understand the effects of returning diagnostic sequencing results on clinical actions and economic outcomes for pediatric patients with suspected genetic disorders. The results showed that patients with positive findings were more likely to receive specialist consultation, but there were no significant increases in overall physician services and costs. More large-scale studies are needed to confirm these findings.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kirstine Stochholm, Camilla Holmgard, Shanlee M. Davis, Claus H. Gravholt, Agnethe Berglund
Summary: This study assessed the incidence, prevalence, and age at diagnosis of individuals with 45,X/46,XY mosaicism and described the associated mortality pattern. The study found an increasing incidence of 45,X/46,XY mosaicism in males and a stable incidence in females. Males were diagnosed at an older age than females. Additionally, 45,X/46,XY mosaicism was associated with increased all-cause mortality.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Yunjia Chen, Ender Karaca, Nathaniel H. Robin, Dana Goodloe, Ali Al-Beshri, S. Joy Dean, Anna C. E. Hurst, Andrew J. Carroll, Fady M. Mikhail
Summary: This study confirms the association between DLG2 intragenic deletions and neurodevelopmental disorders, supports the haploinsufficiency of the DLG2 gene, and suggests a potential association between these deletions and congenital anomalies and dysmorphism.
GENETICS IN MEDICINE
(2024)