Review
Biochemistry & Molecular Biology
I. Basak, H. E. Wicky, K. O. McDonald, J. B. Xu, J. E. Palmer, H. L. Best, S. Lefrancois, S. Y. Lee, L. Schoderboeck, S. M. Hughes
Summary: Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is an incurable childhood brain disease caused by mutations in thirteen CLN genes. Mutations in the CLN5 gene lead to a form of variant late-infantile NCL, with widespread protein expression in various tissues. Research on CLN5 helps to understand lysosomal biology and develop efficient therapies for CLN5 Batten disease.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Endocrinology & Metabolism
Margaux C. Masten, Camille Corre, Alex R. Paciorkowski, Amy Vierhile, Heather R. Adams, Jennifer Vermilion, Grace A. Zimmerman, Erika F. Augustine, Jonathan W. Mink
Summary: A hierarchical diagnostic confidence scheme for CLN3 disease was developed based on genotype and phenotype data from an ongoing natural history study, with excellent face validity shown in a blinded reclassification study. The scheme included four major classes, with individuals further divided into subclasses based on phenotype within the Definite and Probable CLN3 disease classes. Test-retest reliability showed 96% agreement, providing a reliable basis for the diagnosis of CLN3 disease.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Review
Clinical Neurology
Keigo Takahashi, Hemanth R. Nelvagal, Jenny Lange, Jonathan D. Cooper
Summary: This article summarizes the latest understanding of glial pathologies and their contribution to the pathogenesis of NCLs, highlighting the challenges that require further research.
FRONTIERS IN NEUROLOGY
(2022)
Review
Clinical Neurology
Emily Gardner, Sara E. Mole
Summary: Neuronal ceroid lipofuscinoses are a group of inherited neurodegenerative disorders affecting children and adults, sharing similar clinical features and accumulation of storage material. Over 530 mutations have been identified in 13 genes, encoding various proteins including lysosomal enzymes. While many mutations are associated with typical disease phenotypes, there is an increasing description of variant disease phenotypes.
FRONTIERS IN NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hannah L. Best, Alison J. Clare, Kirstin O. McDonald, Hollie E. Wicky, Stephanie M. Hughes
Summary: Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited childhood neurodegenerative disorders characterized by neuroinflammation and alterations in the extracellular environment. This study investigated the secretome in the CLN6 variant of NCL and found significant changes that could be partially corrected with gene therapy, suggesting potential biomarkers for disease monitoring. Overall, the secretome plays a role in CLN6 pathogenesis and may serve as an in vitro model for future studies.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Nouf N. Laqtom, Wentao Dong, Uche N. Medoh, Andrew L. Cangelosi, Vimisha Dharamdasani, Sze Ham Chan, Tenzin Kunchok, Caroline A. Lewis, Ivonne Heinze, Rachel Tang, Christian Grimm, An N. Dang Do, Forbes D. Porter, Alessandro Ori, David M. Sabatini, Monther Abu-Remaileh
Summary: Lysosomes play crucial roles in cellular function, and dysfunction is associated with various human diseases. The study reveals the importance of CLN3 protein in glycerophospholipid metabolism within lysosomes, as its loss leads to massive accumulation of GPDs.
Article
Neurosciences
Yoshiko Munesue, Naohide Ageyama, Nobuyuki Kimura, Ichiro Takahashi, Shunya Nakayama, Sachi Okabayashi, Yuko Katakai, Hiroshi Koie, Ken-ichi Yagami, Kazuhiro Ishii, Akira Tamaoka, Yasuhiro Yasutomi, Nobuhiro Shimozawa
Summary: We report the discovery of cynomolgus macaques carrying the CLN2/TPP1 variant and confirm their neurodegenerative symptoms, which could serve as a new non-human primate model for NCL type 2 disease. These macaques exhibited progressive neuronal clinical symptoms and showed significant cerebellar and cerebral atrophy in the gray matter. Histopathological analysis revealed severe neuronal loss and degeneration, as well as the presence of ceroid-lipofuscin in neurons.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Cell Biology
Shyong Quan Yap, William D. Kim, Robert J. Huber
Summary: The transmembrane protein MFSD8 plays a crucial role in transporting chloride ions across the lysosomal membrane and is associated with CLN7 disease. The ortholog of human MFSD8 in D. discoideum, called mfsd8, is involved in endocytosis, protein secretion, and growth and early development processes. Loss of mfsd8 in D. discoideum leads to increased proliferation, pinocytosis, and cell size, as well as inhibition of cytokinesis and altered enzyme activity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
William D. Kim, Morgan L. D. M. Wilson-Smillie, Aruban Thanabalasingam, Stephane Lefrancois, Susan L. Cotman, Robert J. Huber
Summary: This review summarizes the research linking the autophagy pathway to neuronal ceroid lipofuscinoses (NCLs) and provides guidance for future studies on the contribution of altered autophagy to NCL pathology.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Robert J. J. Huber
Summary: Ceroid lipofuscinosis neuronal (CLN) genes encode 13 proteins that play a role in regulating cellular processes in the endomembrane system. Mutations in CLN genes cause neuronal ceroid lipofuscinosis (NCL), a severe neurodegenerative disease. This review summarizes the current understanding of CLN gene and protein networking in mammalian cells, with a focus on identifying new molecular targets for therapy development. Interestingly, CLN genes and proteins have also been linked to other forms of neurodegeneration, such as Alzheimer's disease and Parkinson's disease, suggesting potential insights into related diseases.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Clinical Neurology
Giancarlo Todiere, Stefania Della Vecchia, Maria Aurora Morales, Andrea Barison, Ivana Ricca, Alessandra Tessa, Elisa Colombi, Filippo Maria Santorelli
Summary: Cardiac MRI is essential for diagnosing hypertrophic cardiomyopathy and may play a role in neuronal ceroid lipofuscinosis, allowing for early diagnosis and treatment monitoring.
FRONTIERS IN NEUROLOGY
(2022)
Article
Cell Biology
Meagan D. McLaren, Sabateeshan Mathavarajah, William D. Kim, Shyong Q. Yap, Robert J. Huber
Summary: The study reveals the important roles of CLN5 in growth and development processes, with CLN5 deficiency affecting cell proliferation, viability, and autophagic flux. Loss of CLN5 in the early stages of multicellular development impacts cell aggregation and autophagic levels. Post-mound formation, CLN5 deficiency results in developmental abnormalities affecting spore morphology, germination, and viability.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Clinical Neurology
H. R. Nelvagal, J. T. Dearborn, J. R. Ostergaard, M. S. Sands, J. D. Cooper
Summary: This study investigated the early pathology of CLN1 disease in the spinal cord of Ppt1-deficient mice, revealing significant microglial activation at 1 month, followed by astrocytosis and other changes at 2 months, and accumulation of storage material and lymphocyte infiltration at 3 months. Inflammatory cytokine expression was altered as early as one month. Behavioral abnormalities were observed at 2 months before a decline in overall locomotor performance. Early onset of the disease 2 months earlier than expected indicates the need for therapies during the presymptomatic period.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Review
Cell Biology
Marcel Klein, Guido Hermey
Summary: Evidence from genetics and cellular and animal models suggests a link between early and late neurodegenerative disorders. This review summarizes the connection between Alzheimer's disease and neuronal ceroid lipofuscinoses. Genetic studies have found overlapping mutations between clinically diagnosed Alzheimer's and neuronal ceroid lipofuscinoses. Dysfunctions in intracellular trafficking mechanisms and the autophagy-endolysosome system are believed to be shared cytopathological processes. Understanding these common mechanisms is important for finding therapeutic targets and tailored treatments.
NEURAL REGENERATION RESEARCH
(2023)
Article
Genetics & Heredity
William D. D. Kim, Robert J. J. Huber
Summary: Mutations in CLN5 cause CLN5 disease, a subtype of neuronal ceroid lipofuscinosis (NCL). In this study, evidence from the model organism Dictyostelium discoideum revealed that loss of the CLN5 homolog, cln5, impacts various cellular and developmental processes. Comparative transcriptomics analysis identified differentially expressed genes and altered enzyme activities in cln5-deficient cells. Additionally, changes in the intracellular and extracellular amounts of specific proteins were observed. Overall, this study provides insights into the molecular mechanisms underlying CLN5 disease and the genes and proteins involved in CLN5-dependent processes.
FRONTIERS IN GENETICS
(2022)
Article
Clinical Neurology
Eline M. C. Hamilton, Pinar Tekturk, Fia Cialdella, Diane F. van Rappard, Nicole I. Wolf, Cengiz Yalcinkaya, Umran Cetincelik, Ahmad Rajaee, Ariana Kariminejad, Justyna Paprocka, Zuhal Yapici, Vlatka Mejaski Bosnjak, Marjo S. van der Knaap
Article
Medicine, General & Internal
Angela Schulz, Temitayo Ajayi, Nicola Specchio, Emily de Los Reyes, Paul Gissen, Douglas Ballon, Jonathan P. Dyke, Heather Cahan, Peter Slasor, David Jacoby, Alfried Kohlschutter
NEW ENGLAND JOURNAL OF MEDICINE
(2018)
Article
Clinical Neurology
Josefine Radke, Randi Koll, Esther Gill, Lars Wiese, Angela Schulz, Alfried Kohlschuetter, Markus Schuelke, Christian Hagel, Werner Stenzel, Hans H. Goebel
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2018)
Article
Clinical Neurology
Alfried Kohlschuetter, Angela Schulz, Udo Bartsch, Stephan Storch
Meeting Abstract
Endocrinology & Metabolism
Zoltan Lukacs, Miriam Nickel, Simona Murko, Paulina Nieves Cobos, Angela Schulz, Rene Santer, Alfried Kohlschuetter
MOLECULAR GENETICS AND METABOLISM
(2019)
Article
Medical Laboratory Technology
Zoltan Lukacs, Miriam Nickel, Simona Murko, Paulina Nieves Cobos, Angela Schulz, Rene Santer, Alfried Kohlschuetter
CLINICA CHIMICA ACTA
(2019)
Article
Clinical Neurology
Alfried Kohlschuetter, Barbara Finckh, Miriam Nickel, Annette Bley, Christoph Huebner
NEURODEGENERATIVE DISEASES
(2020)
Article
Biochemical Research Methods
Stefan Maeser, Brindusa-Alina Petre, Laura Ion, Stephan Rawer, Alfried Kohlschuetter, Filippo M. Santorelli, Alessandro Simonati, Angela Schulz, Michael Przybylski
Summary: The study aimed to develop specific and sensitive diagnostic assays for NCLs, especially with the emergence of enzyme replacement therapy for NCL2 in clinical treatment and ongoing development for other NCLs.
JOURNAL OF MASS SPECTROMETRY
(2021)
Article
Ophthalmology
Yevgeniya Atiskova, Alfried Kohlschutter, Martin Stephan Spitzer, Simon Dulz
Summary: Neuronal ceroid lipofuscinoses are inherited lysosomal storage diseases that can result in progressive neurodegeneration. Visual decline may be the initial symptom, and early diagnosis is crucial for personal and family planning as well as therapeutic strategies. Collaboration with neuropediatricians is recommended when retinal degeneration due to an NCL disease is suspected.
Article
Multidisciplinary Sciences
Nejat Mahdieh, Mahdieh Soveizi, Ali Reza Tavasoli, Ali Rabbani, Mahmoud Reza Ashrafi, Alfried Kohlschuetter, Bahareh Rabbani
Summary: This study evaluated the genetic spectrum of leukodystrophies and leukoencephalopathies in Iran, identifying 35 different types of genetic disorders. Genetic analysis at earlier stages of the disease can reduce uncertainty, costs, and provide basis for genetic counseling and family planning.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
Annette Bley, Jonas Denecke, Alfried Kohlschuetter, Gerhard Schoen, Sandra Hischke, Philipp Guder, Tatjana Bierhals, Heather Lau, Maja Hempel, Florian S. Eichler
Summary: Canavan disease is a rare and devastating leukodystrophy of early childhood with onset of symptoms between 0-6 months. The early hallmarks of the disease include severe psychomotor disability and macrocephaly developing within the first 18 months of life. Seizures become more frequent over time in most patients. Ethnically, CD occurs more frequently outside Ashkenazi Jewish communities than previously reported, and a CD severity score has been developed for assessment of disease severity.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Review
Clinical Neurology
Alfried Kohlschuetter
Summary: The management of Neuronal Ceroid Lipofuscinoses (NCL) presents ethical dilemmas in terms of patient care and treatment decisions, with concerns about end-of-life care planning and potential risks associated with novel therapies. Careful evaluation and consideration of risks and benefits are essential in addressing these ethical issues in the context of rare progressive brain diseases like NCL.
FRONTIERS IN NEUROLOGY
(2021)
Article
Health Policy & Services
Alfried Kohlschuetter, Hendrik van den Bussche
ZEITSCHRIFT FUR EVIDENZ FORTBILDUNG UND QUALITAET IM GESUNDHEITSWESEN
(2019)
Article
Clinical Neurology
Cas Simons, David Dyment, Stephen J. Bent, Joanna Crawford, Marc D'Hooghe, Alfried Kohlschuetter, Sunita Venkateswaran, Guy Helman, Bwee-Tien Poll-The, Christine C. Makowski, Yoko Ito, Kristin Kernohan, Taila Hartley, Quinten Waisfisz, Ryan J. Taft, Marjo S. van der Knaap, Nicole I. Wolf
Article
Pediatrics
Miriam Nickel, Alessandro Simonati, David Jacoby, Susanne Lezius, Dirk Kilian, Benjamin Van de Graaf, Odelya E. Pagovich, Barry Kosofsky, Kaleb Yohay, Matthew Downs, Peter Slasor, Temitayo Aiayi, Ronald G. Crystal, Alfried Kohlschuetter, Dolan Sondhi, Angela Schulz
LANCET CHILD & ADOLESCENT HEALTH
(2018)
Review
Biochemistry & Molecular Biology
M. T. Ciubuc-Batcu, N. J. C. Stapelberg, J. P. Headrick, G. M. C. Renshaw
Summary: The nervous system relies on mitochondria, and impaired mitochondrial function is associated with major depressive disorder. Modulating mitochondrial function may be a therapeutic target for treating MDD.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Correction
Biochemistry & Molecular Biology
Saowaluk Saisomboon, Ryusho Kariya, Piyanard Boonnate, Kanlayanee Sawanyawisuth, Ubon Cha'on, Vor Luvira, Yaovalux Chamgramol, Chawalit Pairojkul, Wunchana Seubwai, Atit Silsirivanit, Sopit Wongkham, Seiji Okada, Sarawut Jitrapakdee, Kulthida Vaeteewoottacharn
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Pavan Thapak, Zhe Ying, Victoria Palafox-Sanchez, Guanglin Zhang, Xia Yang, Fernando Gomez-Pinilla
Summary: Traumatic brain injury (TBI) impairs cellular energy demand, compromising neuronal function and plasticity. This study demonstrates that the mitochondrial activator humanin (HN) can counteract the reduction in mitochondrial bioenergetics caused by TBI, restore memory function and synaptic protein levels, and suppress inflammation and astrocyte proliferation. HN plays an integral role in normalizing fundamental aspects of TBI pathology.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
M. Paul Murphy, Valeria A. Buzinova, Carrie E. Johnson
Summary: Progress has been made in the treatment of Alzheimer's disease through the development of anti-A beta therapeutics, which have shown modest efficacy in slowing the progression of the disease. However, the puzzling issue remains as to why completely removing A beta does not fully stop the disease.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Review
Biochemistry & Molecular Biology
Yang Zhang, Mengqiu Hao, Xuyang Yang, Su Zhang, Junhong Han, Ziqiang Wang, Hai-Ning Chen
Summary: Colorectal cancer often requires adjuvant therapies to reduce tumor burden, and the efficacy of these therapies is significantly influenced by reactive oxygen species (ROS). ROS-mediated colorectal cancer adjuvant therapies involve multiple mechanisms, and preliminary clinical trials have shown the potential of ROS-manipulating therapy in enhancing treatment outcomes.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Mengxin Li, Xuanzhong Wang, Xuyang Chen, Jinghui Hong, Ye Du, Dong Song
Summary: Pancreatic adenocarcinoma (PAAD) is a common digestive malignant tumor with limited treatment options. This study demonstrates that TGM2 may serve as a marker for treatment and prognosis in pancreatic cancer patients. Co-treatment of low dose cisplatin (DDP) and the TGM2 inhibitor GK921 effectively inhibits PAAD cell viability and proliferation in vitro and in vivo, by inhibiting epithelial-to-mesenchymal transition (EMT) induced by TGM2 and enhancing cell cycle arrest and apoptosis caused by DDP. These findings suggest that the combination of GK921 and DDP holds promise as a treatment for PAAD patients.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Liaoran Niu, Qi Wang, Fan Feng, Wanli Yang, Zhenyu Xie, Gaozan Zheng, Wei Zhou, Lili Duan, Kunli Du, Yiding Li, Ye Tian, Junfeng Chen, Qibin Xie, Aqiang Fan, Hanjun Dan, Jinqiang Liu, Daiming Fan, Liu Hong, Jian Zhang, Jianyong Zheng
Summary: This review provides a comprehensive summary of the interaction between cancer cells and macrophages in the tumor microenvironment, and discusses the role of small extracellular vesicles (sEVs) in this process. It also explores the various effects of macrophage-secreted sEVs on tumor malignant transformation, and addresses the therapeutic advancements and challenges associated with these vesicles.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Neha Sawant, Sudhir Kshirsagar, P. Hemachandra Reddy, Arubala P. Reddy
Summary: Depression is a common neuropsychiatric comorbidity in Alzheimer's disease (AD) and other Tauopathies. Selective serotonin reuptake inhibitor (SSRI) treatment, such as Citalopram, not only has anti-depressive and anxiolytic effects, but also helps improve neurogenesis, reduce amyloid burden & Tau pathologies, and neuroinflammation in AD. In this study, Citalopram was found to reduce pathologically pTau level, increase synaptic gene expression and cytoskeletal structure, as well as improve cell survival, mitochondrial respiration, and mitochondrial morphology in cells expressing mutant APP and Tau. These findings suggest that Citalopram could be a promising therapeutic drug for treating depression and AD.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Yueqi Chen, Jiulin Tan, Chuan Yang, Zhiguo Ling, Jianzhong Xu, Dong Sun, Fei Luo
Summary: Bone is a self-healing organ that undergoes continuous regeneration through the cooperation of osteoclasts and osteoblasts. This study used ATAC-seq and RNA-Seq techniques to investigate the chromatin accessibility and transcriptomic landscape of osteoblast differentiation and mineralization. The results showed that global chromatin accessibility was extensively improved during osteoblastogenesis. Additionally, several transcription factors including MEF2A, PRRX1, Shox2, and HOXB13 were found to modulate the promoter accessibility of target genes during osteoblast differentiation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Zi-Ran Kang, Shanshan Jiang, Ji-Xuan Han, Yaqi Gao, Yile Xie, Jinxian Chen, Qiang Liu, Jun Yu, Xin Zhao, Jie Hong, Haoyan Chen, Ying-Xuan Chen, Huimin Chen, Jing-Yuan Fang
Summary: The study demonstrates that BCAA metabolism is involved in the development of colorectal cancer (CRC). BCAT2 deficiency promotes CRC progression by inhibiting BCAA metabolism and chronically activating the mTORC1 pathway.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Chao Zheng, Lingling Liu, Caiyun Liu, Fengna Chu, Yue Lang, Shan Liu, Yan Mi, Jie Zhu, Tao Jin
Summary: Inducing tolerogenic dendritic cells (tDCs) with low RelB expression could effectively alleviate symptoms and reduce immune cell infiltration and demyelination in experimental autoimmune encephalomyelitis (EAE) mouse model.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Hang Lam Li, Simei Go, Jung-Chin Chang, Arthur Verhoeven, Ronald Oude Elferink
Summary: This review highlights the distinct characteristics and crucial role of soluble adenylyl cyclase (sAC) in cellular processes, as well as recent significant advancements in the field of sAC research.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
M. Seco-Cervera, D. Ortiz-Masia, D. C. Macias-Ceja, S. Coll, L. Gisbert-Ferrandiz, J. Cosin-Roger, C. Bauset, M. Ortega, B. Heras-Moran, F. Navarro-Vicente, M. Millan, J. V. Esplugues, S. Calatayud, M. D. Barrachina
Summary: The study revealed the presence of resistance to apoptosis in complicated ileal Crohn's disease, with PDGFB inducing an ETS1-mediated resistance to apoptosis associated with an inflammatory and fibrogenic pattern of expression in intestinal fibroblasts. Potential targets against ileal fibrosis include PDGFRB, IL1R1, or MCL1.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Review
Biochemistry & Molecular Biology
Yunmeng Wang, Ping Cheng
Summary: Oncolytic viruses (OVs) are emerging as therapeutically relevant anticancer agents, especially when combined with genetically modified bispecific T cell engagers (BiTEs). This combination strategy can overcome the limitations of BiTEs alone and provide targeted cytotoxicity to solid tumors.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Stephanie Tannous, Hassan Y. Naim
Summary: Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive disorder caused by variants in the SI gene. A frameshift mutation called c.273_274delAG (p.Gly92Leufs*8) has been identified in CSID patients in Greenlandic population, which leads to loss of digestive function of SI. Surprisingly, the truncated mutant can still be located on the cell surface and interacts with wild type SI, negatively affecting its enzymatic function. Furthermore, heterozygote carriers of this mutation may also exhibit CSID symptoms.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)