Review
Endocrinology & Metabolism
Feixia Zhan, Xiaoli Liu, Ruilong Ni, Taotao Liu, Yuwen Cao, Jingying Wu, Wotu Tian, Xinghua Luan, Li Cao
Summary: Multiple mitochondrial dysfunction syndrome (MMDS) is a group of mitochondrial diseases caused by nuclear gene mutations, characterized by early onset, impaired neurological development, muscle weakness, and other symptoms. There are six identified types based on different genotypes, including IBA57 which encodes a protein crucial for mitochondrial enzyme activity.
METABOLIC BRAIN DISEASE
(2022)
Review
Genetics & Heredity
Steven H. Lang, Francesca Camponeschi, Evan de Joya, Paulo Borjas-Mendoza, Mustafa Tekin, Willa Thorson
Summary: This study reports a case of MDDS3 in a 2-month-old Cuban infant, who carries a homozygous variant in the IBA57 gene. The variant is located in a putative mutational hotspot. In order to gain a clearer understanding of the typical presentation of MDDS3, the study reviewed 52 cases from the literature.
Article
Clinical Neurology
Liwen Wu, Xiangfu Liao, Sai Yang, Siyi Gan
Summary: This study presented a pedigree with three children displaying global developmental retardation, white matter lesions, and cerebellar dentate nucleus involvement, caused by mutations in GALC and NDUFAF1 genes. The parents carried the mutations as heterozygous states, indicating a polygenic inheritance pattern. Comprehensive analysis of clinical phenotypes, gene functions, and family history is crucial for accurate diagnosis and management.
FRONTIERS IN NEUROLOGY
(2021)
Article
Genetics & Heredity
Rita Alfattal, Maryam Alfarhan, Adeeb M. Algaith, Buthaina Albash, Reem M. Elshafie, Asma Alshammari, Ahmad Alahmad, Fatima Dashti, Rasha Alsafi, Hind Alsharhan
Summary: Defects in respiratory chain complex III (CIII) lead to rare mitochondrial disorders that have distinct neuroradiological abnormalities. The molecular defects involving mitochondrial CIII assembly factors are still largely unknown. This report presents the clinical and radiological characteristics of a patient with LYRM7-associated mitochondrial leukoencephalopathy, as well as summarizes the previous findings on this condition.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Editorial Material
Critical Care Medicine
Simon Proctor, John Gilbert, Christopher Barnett, Marc Agzarian, Jeffrey J. Bowden
Summary: A 16-year-old boy presented with left iliac fossa pain for 6 days. He had a history of right subtalar dislocation and appendicitis, and his brother died suddenly 3 weeks ago after a 12-month illness with intermittent epigastric pain, weight loss, and hemoptysis. He had traveled to the Philippines 3 years ago and was hospitalized there for appendicitis.
Article
Multidisciplinary Sciences
Yiqin Wang, Xiaoxian Guo, Xiumei Hong, Guoying Wang, Colleen Pearson, Barry Zuckerman, Andrew G. Clark, Kimberly O. O'Brien, Xiaobin Wang, Zhenglong Gu
Summary: This study investigates the role of mitochondrial genome (mtDNA) in autism spectrum disorder (ASD) risk, and finds that mutations in mtDNA are associated with increased ASD risk in children, and the heteroplasmies in parents have different effects in ASD children.
NATURE COMMUNICATIONS
(2022)
Article
Clinical Neurology
Yingjie Li, Jiaming Xu, Yan Xu, Chuanzhou Li, Yan Wu, Zhijun Liu
Summary: This study aimed to characterize the clinical and genetic features of leukodystrophies in a Chinese cohort. Pathogenic variants in several genes were identified, and the functional analysis of these mutations provided insights into the pathogenic mechanisms of CSF1R-related leukodystrophy.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Natalia Todosenko, Olga Khaziakhmatova, Vladimir Malashchenko, Kristina Yurova, Maria Bograya, Maria Beletskaya, Maria Vulf, Natalia Gazatova, Larisa Litvinova
Summary: Metabolic syndrome acts as a precursor to major health diseases such as cardiovascular disease and diabetes, which have high mortality rates in industrialized countries. Mitochondrial dysfunction plays a crucial role in the pathogenesis of metabolic syndrome, leading to tissue hypoxia, disruption of mitochondrial integrity, increased production of reactive oxygen species, and decreased ATP levels, resulting in chronic inflammation affecting tissues and organs. The mitochondrial protease Lon (Lonp1) shows potential as a molecular target for the development of targeted therapy for metabolic syndrome and its components due to its broad spectrum of activities, including protein degradation, chaperone activity, and mitochondrial DNA binding.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Dafne Suraci, Giovanni Saudino, Veronica Nasta, Simone Ciofi-Baffoni, Lucia Banci
Summary: The study reveals the coordinated mechanism of ISCA1, ISCA2, and NFU1 in the maturation process of mitochondrial [4Fe-4S] proteins. ISCA1 plays a key role in promoting the interaction between NFU1 and ISCA2, leading to the formation of a transient ISCA1-ISCA2-NFU1 ternary complex. This mechanism ensures the safe transfer of [4Fe-4S] clusters from the assembly site on the ISCA1-ISCA2 complex to NFU1, making them available for mitochondrial apo proteins that require NFU1.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Stefano Da Vela, Giovanni Saudino, Francesca Lucarelli, Lucia Banci, Dmitri I. Svergun, Simone Ciofi-Baffoni
Summary: In humans, the biosynthesis and trafficking of mitochondrial [4Fe-4S]2+ clusters is a highly coordinated process that requires a complex protein machinery. Two [2Fe-2S]2+ clusters are converted into a [4Fe-4S]2+ cluster on an ISCA1-ISCA2 complex. NFU1 is the accessory protein that first receives the [4Fe-4S]2+ cluster from the ISCA1-ISCA2 complex.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Alexander V. Blagov, Vasily N. Sukhorukov, Alexander N. Orekhov, Margarita A. Sazonova, Alexandra A. Melnichenko
Summary: This article reviews the role of mitochondrial dysfunction in the pathogenesis of multiple sclerosis and proposes new therapeutic strategies to restore mitochondrial function in this disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Jiayin Guo, Xiaoxu Chen, Zhiwei Liu, Haifeng Sun, Yu Zhou, Yichen Dai, Yu'e Ma, Lei He, Xuezhen Qian, Jianying Wang, Jie Zhang, Yichen Zhu, Jun Zhang, Bin Shen, Fei Zhou
Summary: The discovery of DddA-derived cytosine base editor (DdCBE) enables precise manipulation of mtDNA, holding potential for the treatment of mitochondrial disorders. In vivo testing using mouse cells and embryos demonstrated the effectiveness and accuracy of DdCBE in editing mtDNA.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Cardiac & Cardiovascular Systems
Takahiko Kiyooka, Vahagn Ohanyan, Liya Yin, Yuh Fen Pung, Yeong-Renn Chen, Chwen-Lih Chen, Patrick T. Kang, James P. Hardwick, June Yun, Danielle Janota, Joanna Peng, Christopher Kolz, Giacinta Guarini, Glenn Wilson, Inna Shokolenko, Donte A. Stevens, William M. Chilian
Summary: Endothelial dysfunction in diabetes is mainly attributed to impaired mitochondrial function, not just the result of oxidative stress. Restoring mitochondrial function can reverse endothelial dysfunction, indicating the critical role of mitochondrial function in endothelium-dependent vasodilation.
BASIC RESEARCH IN CARDIOLOGY
(2022)
Article
Cell Biology
Alberto Danese, Simone Patergnani, Alessandra Maresca, Camille Peron, Andrea Raimondi, Leonardo Caporali, Saverio Marchi, Chiara La Morgia, Valentina Del Dotto, Claudia Zanna, Angelo Iannielli, Alice Segnali, Ivano Di Meo, Andrea Cavaliere, Magdalena Lebiedzinska-Arciszewska, Mariusz R. Wieckowski, Andrea Martinuzzi, Milton N. Moraes-Filho, Solange R. Salomao, Adriana Berezovsky, Rubens Belfort, Christopher Buser, Fred N. Ross-Cisneros, Alfredo A. Sadun, Carlo Tacchetti, Vania Broccoli, Carlotta Giorgi, Valeria Tiranti, Valerio Carelli, Paolo Pinton
Summary: Patients with Leber's hereditary optic neuropathy (LHON) exhibit sustained abnormal autophagy and compartment-specific mitophagy activity, disrupting mitochondrial homeostasis and leading to defective bioenergetics and excessive reactive oxygen species production. Modulating autophagy and mitochondrial biogenesis can counteract this pathological mechanism.
Article
Clinical Neurology
S. D. Roosendaal, T. van de Brug, C. A. P. F. Alves, S. Blaser, A. Vanderver, N. Wolf, M. S. van der Knaap
Summary: Through MRI evaluation of 132 patients with known genetic defects in mitochondrial leukodystrophy, common features associated with mitochondrial disease were identified, along with specific MRI patterns correlating with certain genotypes.
AMERICAN JOURNAL OF NEURORADIOLOGY
(2021)
Review
Neurosciences
Chiara Reale, Federica Invernizzi, Celeste Panteghini, Barbara Garavaglia
Summary: This review provides an overview of how sex and gender affect disease development, emphasizing the importance of understanding gender differences in promoting personalized care. It highlights the role of genetic differences and clinical manifestations in neurological diseases such as Alzheimer's disease, Parkinson's disease, and obsessive-compulsive disorder.
JOURNAL OF NEUROSCIENCE RESEARCH
(2023)
Letter
Genetics & Heredity
Alessandra Torraco, Reza Maroofian, Agnes Rotig, Enrico Bertini, Daniele Ghezzi, Rosalba Carrozzo, Daria Diodato
Review
Biochemistry & Molecular Biology
Massimo Zeviani, Valerio Carelli
Summary: The retina is a vulnerable target for defects in oxidative phosphorylation (OXPHOS) due to mitochondrial impairment, resulting in conditions such as retinal dystrophy and optic atrophy. Mutations in mitochondrial DNA (mtDNA) and nuclear genes are implicated in mitochondrial retinopathies, presenting as isolated diseases or part of more complex syndromes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Alessia Nasca, Niccolo E. Mencacci, Federica Invernizzi, Michael Zech, Ignacio J. Keller Sarmiento, Andrea Legati, Chiara Frascarelli, Bernabe Bustos, Luigi M. Romito, Dimitri Krainc, Juliane Winkelmann, Miryam Carecchio, Nardo Nardocci, Giovanna Zorzi, Holger Prokisch, Steven J. Lubbe, Barbara Garavaglia, Daniele Ghezzi
Summary: Nasca et al. have discovered a new candidate gene for dystonia, ATP5F1B, which encodes a subunit of the mitochondrial ATP synthase. This gene is associated with early-onset isolated dystonia in two families with autosomal dominant inheritance and incomplete penetrance. Functional studies showed a dominant-negative effect of the identified ATP5F1B variants, leading to reduced activity of complex V and impaired mitochondrial function.
Article
Clinical Neurology
Anna Ardissone, Giulia Ferrera, Costanza Lamperti, Valeria Tiranti, Daniele Ghezzi, Isabella Moroni, Eleonora Lamantea
Summary: This study reviewed the data of 150 pediatric patients with mitochondrial diseases (MDs) due to mtDNA alterations collected over the past 20 years. The results showed that mtDNA impairment is less common than nDNA impairment in pediatric MDs. Ocular involvement, especially classical Leber hereditary optic neuropathy, was extremely frequent in this cohort, particularly with onset before 12 years of age. Unlike adult phenotypes, extraneurological manifestations and isolated myopathy were rare. Deep gray matter involvement, early disease onset, and specific phenotypes such as Pearson syndrome and Leigh syndrome were found to be unfavorable prognostic factors. Phenotypes related to single large scale mtDNA deletions were very frequent in the pediatric population. Furthermore, the study reported for the first time an mtDNA pathogenic variant associated with cavitating leukodystrophy.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Letter
Clinical Neurology
Sara Satolli, Federica Invernizzi, Federica Rachele Danti, Chiara Reale, Celeste Panteghini, Nardo Nardocci, Barbara Garavaglia, Giovanna Zorzi
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Biochemistry & Molecular Biology
Mirko Baglivo, Alessia Nasca, Eleonora Lamantea, Stefano Vinci, Manuela Spagnolo, Silvia Marchet, Holger Prokisch, Alessia Catania, Costanza Lamperti, Daniele Ghezzi
Summary: Leber's hereditary optic neuropathy (LHON) is a disease that causes visual loss due to damage to the optical nerve. In this study, the respiratory parameters of LHON patients' fibroblasts were evaluated, revealing reduced respiration in untreated conditions and no significant improvement after idebenone supplementation. The responsiveness of cultured cells to idebenone treatment did not fully reflect in vivo data, indicating the need for further evaluation of cellular respiration as a potential biomarker for LHON prognosis and treatment response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Alessio Di Fonzo, Marco Percetti, Edoardo Monfrini, Ilaria Palmieri, Alberto Albanese, Micol Avenali, Anna Bartoletti-Stella, Fabio Blandini, Gloria Brescia, Giovanna Calandra-Buonaura, Rosa Campopiano, Sabina Capellari, Isabel Colangelo, Giacomo Pietro Comi, Giada Cuconato, Rosangela Ferese, Caterina Galandra, Stefano Gambardella, Barbara Garavaglia, Andrea Gaudio, Emiliano Giardina, Federica Invernizzi, Paola Mandich, Rossana Mineri, Celeste Panteghini, Chiara Reale, Lucia Trevisan, Stefania Zampatti, Pietro Cortelli, Enza Maria Valente
Summary: This study attempts to harmonize the reporting of PD genetic testing across multiple diagnostic labs and highlights the current challenges in interpreting genetic variants from NGS-multigene panels, which has significant implications for counseling.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Celeste Panteghini, Chiara Reale, Isabel Colangelo, Marta Suerz, Alessia Catania, Barbara Garavaglia, Federica Invernizzi
Summary: In this study, we found that screening the entire GBA1 gene with specific techniques increases the diagnostic rate of Parkinson's disease. Males have a higher frequency of severe variants and complex alleles, while mild variants are equally distributed in both sexes, and risk variants are more common in females.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Genetics & Heredity
Federica Invernizzi, Rossella Izzo, Isabel Colangelo, Andrea Legati, Nadia Zanetti, Barbara Garavaglia, Eleonora Lamantea, Lorenzo Peverelli, Anna Ardissone, Isabella Moroni, Lorenzo Maggi, Silvia Bonanno, Laura Fiori, Daniele Velardo, Francesca Magri, Giacomo P. Comi, Dario Ronchi, Daniele Ghezzi, Costanza Lamperti
Summary: This study aimed to investigate the possible genetic causes of recurrent hyperCKemia or clinical suspicion of inherited metabolic myopathy. A cohort of 139 patients was analyzed and a genetic diagnosis was obtained in 15.1% of cases, while candidate variants or variants of uncertain significance were found in a further 39.5%. The results confirmed the high genetic heterogeneity of hyperCKemia and metabolic myopathies, suggesting the existence of additional genes associated with this condition and the possibility of cases being caused by extrinsic factors.
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.
Article
Clinical Neurology
Alberto A. Zambon, Daniele Ghezzi, Cristina Baldoli, Gianni Cutillo, Katia Fontana, Valentina Sofia, Maria Grazia Patricelli, Alessia Nasca, Stefano Vinci, Ivana Spiga, Eleonora Lamantea, Giovanna F. Fanelli, Maria Grazia Natali Sora, Rosanna Rovelli, Antonella Poloniato, Paola Carrera, Massimo Filippi, Graziano Barera
Summary: This study presents a novel phenotype associated with AIFM1 and reviews the existing literature on AIFM1-related disorders. Through various tests and studies, a pathogenic variant in the AIFM1 gene was identified and its effects on cellular function were observed. The patient exhibited drug-resistant, electro-clinical, multifocal seizures shortly after birth, and brain MRI revealed brain swelling and signal alteration in specific areas. Functional studies on cultured fibroblasts showed a reduction in AIFM1 protein amount and defective activities of respiratory chain complexes.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)