Article
Pediatrics
Chaoping Hu, Yiyun Shi, Lei Zhao, Shuizhen Zhou, Xihua Li
Summary: This study reported five Chinese MC patients with CLCN1 mutations, expanding the clinical and genetic spectrum. Literature review revealed that variants in exon 8 were most prevalent among Chinese MC patients, with c.892G>A (p.A298T) possibly being a founder mutation.
FRONTIERS IN PEDIATRICS
(2021)
Article
Biochemistry & Molecular Biology
Yifan Li, Mao Li, Zhenfu Wang, Fei Yang, Hongfen Wang, Xiujuan Bai, Bo Sun, Siyu Chen, Xusheng Huang
Summary: In this study, we reported the clinical and molecular characteristics of six patients with Myotonia congenita (MC) and reviewed the literature on Chinese people. Our findings showed that the clinical phenotype of MC in Chinese people is similar to that found in the West, while the genotype is different. This study expands the understanding of the clinical and genetic spectrum of MC in the Chinese population.
Article
Pharmacology & Pharmacy
Concetta Altamura, Elena Conte, Carmen Campanale, Paola Laghetti, Ilaria Saltarella, Giulia Maria Camerino, Paola Imbrici, Jean-Francois Desaphy
Summary: This study found that niflumic acid (NFA) can act as a pharmacological chaperone and has therapeutic effects on patients with specific ClC-1 channel mutations in myotonia congenita (MC). NFA can improve the expression of ClC-1 protein on the plasma membrane to restore normal chloride ion channel function.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Dermatology
Weilong Zhong, Linghan Hu, Xu Cao, Jiahui Zhao, Xianning Zhang, Mingyang Lee, Huijun Wang, Jie Zhang, Quan Chen, Cheng Feng, Lina Duo, Xiuli Wang, Li Tang, Zhimiao Lin, Yong Yang
Summary: The study identified new and recurrent variations in the TRPV3 gene in patients with Olmsted syndrome, finding that variations in specific regions of the gene significantly enhance channel function and lead to severe phenotypes, while other variations have milder effects.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Endocrinology & Metabolism
Peng Tang, Jun Zhang, Song Peng, Yapeng Wang, Haoyang Li, Ze Wang, Yao Zhang, Yiqiang Huang, Jing Xu, Dianzheng Zhang, Qiuli Liu, Luofu Wang, Weihua Lan, Jun Jiang
Summary: 21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia. This study analyzed 15 patients from three families and found that different phenotypes were caused by different CYP21A2 mutations. Gender and mutation type influence the phenotypes, and genetic analysis can aid in the diagnosis of atypical 21-hydroxylase deficiency patients.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Etienne Mornet, Agnes Taillandier, Christelle Domingues, Annika Dufour, Emmanuelle Benaloun, Nicole Lavaud, Fabienne Wallon, Nathalie Rousseau, Carole Charle, Mihelaiti Guberto, Christine Muti, Brigitte Simon-Bouy
Summary: The study analyzed a cohort of 424 HPP patients of European origin, classifying ALPL pathogenic variants based on their dominant negative effects and severity. Homozygosity was found to exacerbate severity, with moderate alleles being rare. Pathogenic variants with no dominant negative effect were associated with milder symptoms, suggesting a new clinical entity.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Shangzhi Dai, Huijun Wang, Zhimiao Lin
Summary: Becker's nevus is characterized by hyperpigmentation and hypertrichosis, and recent studies have shown that it is associated with postzygotic ACTB mutations. The majority of BN patients have recurrent mutations in ACTB, although some patients do not have these mutations, indicating genetic heterogeneity. Genotype-phenotype correlation analysis suggests that lesions located above the waistline and covering more than 1% BSA are more likely to be positive for ACTB mutations.
Article
Genetics & Heredity
Alessandro De Falco, Achille Iolascon, Flora Ascione, Carmelo Piscopo
Summary: The use of array comparative genomic hybridization (array-CGH) has identified new microdeletion/microduplication syndromes, including the 9q21.13 microdeletion syndrome. This syndrome involves the loss of a specific genomic region and is associated with developmental delay, intellectual disability, autistic behavior, seizures, facial dysmorphism, myopia, and previously unreported brain anomalies. A study of 28 patients, including our case, allowed for the classification and analysis of candidate genes, as well as the correlation between genotype and phenotype. These findings provide a better understanding of the syndromic spectrum of 9q21.13 microdeletion syndrome and suggest the need for regular ophthalmological and neurological monitoring.
Editorial Material
Plant Sciences
Matthew F. McCabe, Mark Tester
Summary: The convergence of autonomous platforms, advances in machine learning, and rapid sequencing for genome description offer new insights and discoveries in plant sciences. Researchers leverage these tools to bridge the gap between field-based phenotyping and genetic loci identification in the lab, highlighting the need for further collaboration across multidisciplinary fields in digital agriculture.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Article
Cardiac & Cardiovascular Systems
Jonas W. Bartstra, Sara Risseeuw, Pim A. de Jong, Bram van Os, Lianne Kalsbeek, Chris Mol, Annette F. Baas, Shana Verschuere, Olivier Vanakker, Ralph J. Florijn, Jeroen Hendrikse, Willem Mali, Saskia Imhof, Jeannette Ossewaarde-van Norel, Redmer van Leeuwen, Wilko Spiering
Summary: The study revealed that PXE patients with a mixed genotype showed less severe arterial and ophthalmological phenotypes compared to patients with two truncating variants in the ABCC6 gene. Further research into environmental and genetic modifiers may help explain the unexplained phenotypic variability.
Article
Genetics & Heredity
Liyan Wu, Wei Zhang, Yanmeng Li, Donghu Zhou, Bei Zhang, Anjian Xu, Zhen Wu, Lina Wu, Shuxiang Li, Xiaoming Wang, Xinyan Zhao, Qianyi Wang, Min Li, Yu Wang, Hong You, Jian Huang, Xiaojuan Ou, Jidong Jia
Summary: This study is the first comprehensive analysis of the gene variant spectrum and phenotypic aspects of non-HFE HH in China, providing useful insights for the identification, diagnosis, and management of HH in China.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Review
Genetics & Heredity
Yu Fan, Yuming Xu, Changhe Shi
Summary: GGC repeat expansion in NOTCH2NLC is the most common causative factor in neuronal intranuclear inclusion disease in Asians. This expansion has been identified in various other diseases as well, suggesting a link with clinical phenotype.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Geriatrics & Gerontology
Yingzi Liu, Xuewen Xiao, Hui Liu, Xinxin Liao, Yafang Zhou, Ling Weng, Lu Zhou, Xixi Liu, Xiang-yun Bi, Tianyan Xu, Yuan Zhu, Qijie Yang, Sizhe Zhang, Xiaoli Hao, Weiwei Zhang, Junling Wang, Bin Jiao, Lu Shen
Summary: Alzheimer's disease is a progressive neurodegenerative disease associated with aging, environmental, and genetic factors. Mutations in the amyloid protein precursor gene (APP) are known to be pathogenic for familial Alzheimer's disease. Although patients with APP mutations show more non-demented symptoms and neurological symptoms, their clinical phenotypes are generally consistent with typical AD. Genotype-phenotype analysis based on APP processing differences caused by mutations revealed differences in onset age, behavioral and psychological disorders of dementia, and myoclonus.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Sumihito Togi, Hiroki Ura, Hisayo Hatanaka, Yo Niida
Summary: This study analyzed genotype and phenotype of TSC in Japanese patients and found differences in lesions and symptoms between TSC1 and TSC2 patients. It also revealed that 20% of parents of a proband may have mild TSC and more mild neuropsychiatric phenotypes were diagnosed in Japan.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Do Hoon Kwon, Feng Zhang, Brett A. A. McCray, Shasha Feng, Meha Kumar, Jeremy M. M. Sullivan, Wonpil Im, Charlotte J. J. Sumner, Seok-Yong Lee
Summary: The structural basis of the interaction between ion channels and small GTPases is not well understood. This study presents cryo-EM structures of TRPV4 in complex with RhoA, revealing the mechanism of ligand-dependent gating of TRPV4. The results suggest that RhoA acts as an auxiliary subunit for TRPV4, regulating calcium homeostasis, and disruption of TRPV4-RhoA interactions can lead to neuromuscular disease.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Gabriele Carullo, Federica Falbo, Amer Ahmed, Alfonso Trezza, Beatrice Gianibbi, Orazio Nicolotti, Giuseppe Campiani, Francesca Aiello, Simona Saponara, Fabio Fusi
Summary: Three new derivatives (5a-c) that interact with Ca(V)1.2 channels were found using PLATO. These derivatives exhibited better vasorelaxant effects than the parent compound and antagonized electro- and pharmaco-mechanical coupling in an endothelium-independent manner. Compound 5a, the most potent in the series, also reduced Ca2+ mobilization and inhibited Ba2+ current through Ca(V)1.2 channels, but it also inhibited K(Ca)1.1 channel currents in a concentration-dependent manner.
BIOORGANIC CHEMISTRY
(2023)
Article
Clinical Neurology
Mirna Andelic, Erika Salvi, Stefania Marcuzzo, Margherita Marchi, Raffaella Lombardi, Daniele Cartelli, Daniele Cazzato, Elkadia Mehmeti, Andrea Gelemanovic, Matilde Paolini, Carlotta Pardo, Ilaria D'Amato, Janneke G. J. Hoeijmakers, Sulayman Dib-Hajj, Stephen G. Waxman, Catharina G. Faber, Giuseppe Lauria
Summary: Personalized management of neuropathic pain is a clinical need that has not been fulfilled due to various factors. Recent studies on microRNA have provided insights into pain-related mechanisms and identified potential drug candidates. By generating a molecular profile of the epidermis in patients with sodium channel-related painful neuropathy, the researchers identified specific miRNAs and mRNA targets that are involved in peripheral sensory transduction and modulation. The findings suggest a complex interaction between epidermal cells and axons in neuropathy pain. This targeted molecular profiling could advance personalized medicine for neuropathic pain.
Letter
Clinical Neurology
Andreas Meisel, Fulvio Baggi, Anthony Behin, Amelia Evoli, Anna Kostera-Pruszczyk, Renato Mantegazza, Raul Juntas Morales, Anna Rostedt Punga, Sabrina Sacconi, Michael Schroeter, Jan Verschuuren, Louise Crathorne, Kris Holmes, Maria-Isabel Leite
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Chemistry, Medicinal
Maria Vittoria Togo, Fabrizio Mastrolorito, Fulvio Ciriaco, Daniela Trisciuzzi, Anna Rita Tondo, Nicola Gambacorta, Loredana Bellantuono, Alfonso Monaco, Francesco Leonetti, Roberto Bellotti, Cosimo Damiano Altomare, Nicola Amoroso, Orazio Nicolotti
Summary: This article presents a robust and reproducible eXplainable Artificial Intelligence (XAI) approach for predicting developmental toxicity, which is a challenging human-health endpoint in toxicology. The proposed framework compares favorably with state-of-the-art approaches in terms of accuracy, sensitivity, and specificity, providing a reliable support system for ensuring informativeness, uncertainty estimation, generalization, and transparency in developmental toxicity. The model utilizes specific molecular descriptors and structural alerts to distinguish toxic and nontoxic chemicals.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Christos Stergiou, Rhys Williams, Jennifer R. R. Fleming, Vasiliki Zouvelou, Elpinickie Ninou, Francesca Andreetta, Elena Rinaldi, Ornella Simoncini, Renato Mantegazza, Julius Bogomolovas, John Tzartos, Siegfried Labeit, Olga Mayans, Socrates Tzartos
Summary: Myasthenia gravis is an autoimmune disease caused by antibodies targeting the neuromuscular junction of skeletal muscles. The major autoantigen is nicotinic acetylcholine receptor. Thymus and thymoma play critical roles in the mechanisms and management of the disease. This study focused on the localization of titin epitopes to develop more specific anti-titin diagnostics.
Article
Neurosciences
Veria Vacchiano, Raffaella Brugnoni, Carmen Campanale, Paola Imbrici, Giorgia Dinoi, Eleonora Canioni, Paola Laghetti, Ilaria Saltarella, Concetta Altamura, Lorenzo Maggi, Rocco Liguori, Vincenzo Donadio, Jean-Francois Desaphy
Summary: Non-dystrophic myotonias are a group of diseases characterized by muscle stiffness caused by gene mutations in CLCN1 and SCN4A. In this study, the clinical features and genetic variants of five affected relatives were described. Functional experiments revealed that the p.K1302R variant in SCN4A and the p.H838P variant in CLCN1 caused mild changes in sodium and chloride currents, respectively, leading to the mixed myotonic phenotypes observed in the patients. Mexiletine and lamotrigine were found to be effective in treating patients carrying the p.K1302R variant.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Eleonora Giagnorio, Claudia Malacarne, Paola Cavalcante, Letizia Scandiffio, Marco Cattaneo, Viviana Pensato, Cinzia Gellera, Nilo Riva, Angelo Quattrini, Eleonora Dalla Bella, Giuseppe Lauria, Renato Mantegazza, Silvia Bonanno, Stefania Marcuzzo
Summary: Amyotrophic lateral sclerosis (ALS) is characterized by the loss of upper and lower motor neurons (UMNs, LMNs) and miR-146a dysregulation may contribute to the pathogenesis of ALS. In this study, miR-146a levels were increased in ALS peripheral nerves and decreased in the serum of ALS patients, suggesting its potential as a diagnostic and prognostic biomarker for the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Rowida Almomani, Maurice Sopacua, Margherita Marchi, Milena Sleczkowska, Patrick Lindsey, Bianca T. A. de Greef, Janneke G. J. Hoeijmakers, Erika Salvi, Ingemar S. J. Merkies, Maryam A. Ferdousi, Rayaz Malik, Dan Ziegler, Kasper W. J. Derks, Gidon Boenhof, Filippo Martinelli-Boneschi, Daniele Cazzato, Raffaella Lombardi, Sulayman G. Dib-Hajj, Stephen Waxman, Hubert J. M. M. Smeets, Monique G. Gerrits, Catharina Faber, Giuseppe Lauria
Summary: Rare SCG genetic variants may contribute to the development of painful neuropathy. Genetic profiling and SCG variant identification can provide better understanding of the genetic variability in patients with painful and painless neuropathy, leading to improved risk stratification and personalized pain treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Anesthesiology
Margherita Marchi, Erika Salvi, Mirna Andelic, Elkadia Mehmeti, Ilaria D'Amato, Daniele Cazzato, Federica Chiappori, Raffaella Lombardi, Daniele Cartelli, Grazia Devigili, Eleonora Dalla Bella, Monique Gerrits, Rowida Almomani, Rayaz A. Malik, Milena Sleczkowska, Anna Mazzeo, Luca Gentile, Sulayman Dib-Hajj, Stephen G. Waxman, Catharina G. Faber, Eleonora Vecchio, Marina de Tommaso, Giuseppe Lauria
Summary: This study aimed to identify rare variants associated with chronic neuropathic pain and nociplastic pain by conducting next-generation sequencing and gene-wise aggregation analysis. TRPA1 was found to be the most significant gene, with the frequency of rare variants significantly differentiating chronic pain patients from healthy controls. The study expands the understanding of channelopathy-related chronic pain disorders and contributes to personalized therapies based on patients' molecular profiles.
Article
Biochemistry & Molecular Biology
Nicola Iacomino, Letizia Scandiffio, Fabio Conforti, Erika Salvi, Maria Cristina Tarasco, Federica Bortone, Stefania Marcuzzo, Ornella Simoncini, Francesca Andreetta, Daniela Pistillo, Emanuele Voulaz, Marco Alloisio, Carlo Antozzi, Renato Mantegazza, Tommaso Martino De Pas, Paola Cavalcante
Summary: The thymus plays a role in the development of autoimmunity in myasthenia gravis (MG) patients. Changes in gene expression related to muscle autoantigens, such as AChR α subunit (CHRNA1) and autoimmune regulator (AIRE), as well as tumor-related muscle-like proteins (NEFM, HSP60, RYR1, RYR3, TTN), were observed in MG thymuses with hyperplasia and thymoma. These findings suggest a potential mechanism for the development of MG in thymomas involving altered autoantigen expression and molecular mimicry.
Article
Immunology
Cristina Cappelletti, Raffaella Brugnoni, Silvia Bonanno, Francesca Andreetta, Franco Salerno, Eleonora Canioni, Gaetano Nicola Alfio Vattemi, Paola Tonin, Renato Mantegazza, Lorenzo Maggi
Summary: This study aimed to investigate whether the immune system could serve as a source of potential biomarkers for stratifying immune-mediated necrotizing myopathies (IMNMs) subtypes. The results showed a significant preponderance of M1 macrophages in muscle samples of both SRP+ and HMGCR(+) IMNM patients. Furthermore, TLR4 and IL-7 were identified as potential immune biomarkers for differentiating between SRP+ and HMGCR+ patients.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Chemistry, Medicinal
Nicola Gambacorta, Fulvio Ciriaco, Nicola Amoroso, Cosimo Damiano Altomare, Ju''rgen Bajorath, Orazio Nicolotti
Summary: In this study, a CIRCE compound prediction platform was developed based on explainable machine learning to support the design of selective CB1R and CB2R ligands. The platform achieved about 80% accuracy in test calculations and provided rationalized explanations for the predictions. CIRCE is freely available as a web-based prediction platform.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Marco Paolino, Modesto de Candia, Rosa Purgatorio, Marco Catto, Mario Saletti, Anna Rita Tondo, Orazio Nicolotti, Andrea Cappelli, Antonella Brizzi, Claudia Mugnaini, Federico Corelli, Cosimo D. Altomare
Summary: Combining photopharmacology approach with multitarget-directed ligand design strategy, a novel donepezil-like compound was discovered that showed dual inhibition activity against acetylcholinesterase and monoamine oxidase B, two target enzymes related to Alzheimer's disease. Further investigation of similar compounds revealed different selectivity towards the target enzymes.
Review
Genetics & Heredity
Raffaella Brugnoni, Daria Marelli, Nicola Iacomino, Eleonora Canioni, Cristina Cappelletti, Lorenzo Maggi, Anna Ardissone
Summary: Schwartz-Jampel syndrome type 1 (SJS1) is a rare genetic disorder caused by mutations in the HSPG2 gene, resulting in musculoskeletal problems. This study reports two mutations in a Moroccan child with SJS1 and analyzes the clinical features and genetic characteristics of the disease.
Review
Health Care Sciences & Services
Carlo Antozzi, Renato Mantegazza
Summary: Myasthenia gravis is an autoimmune disorder that causes muscle weakness and fatigue. Standard therapies have limitations and there is a need for targeted treatments. Ravulizumab, a long-acting complement inhibitor, has shown effective and sustained improvement in patients with myasthenia gravis.
PATIENT-RELATED OUTCOME MEASURES
(2023)