Review
Clinical Neurology
Simone Aloisio, Sara Satolli, Gabriele Bellini, Piervito Lopriore
Summary: Parkinsonism is a syndrome characterized by bradykinesia accompanied by rest tremor, rigidity, or both. It is commonly seen in Parkinson's disease and atypical parkinsonian disorders. However, it can also be a manifestation of complex neurogenetic diseases. Understanding the clinical features of parkinsonism in adult-onset neurogenetic diseases is important for understanding pathophysiological mechanisms and for clinical diagnosis and treatment.
NEUROLOGICAL SCIENCES
(2023)
Article
Neurosciences
Diana Maria Cubillos-Arcila, Gustavo Dariva Machado, Lauren Sehnem, Daniela Burguez, Ana Paula Janner Zanardi, Valeria Feijo Martins, Leonardo Alexandre Peyre-Tartaruga, Jonas Alex Morales Saute
Summary: The study found that functional gait performance in individuals with HSP was significantly impaired compared to controls, but after 18 months of follow-up, there was no significant difference in TFT performance from baseline, with some tests showing more frequent improvement. TFTs were effective instruments for assessing disease severity, but did not fully capture the very slow motor evolution of HSPs, highlighting the need for additional biomarkers of disease progression.
Review
Biochemistry & Molecular Biology
Arun Meyyazhagan, Antonio Orlacchio
Summary: This review provides an overview of hereditary spastic paraplegia (HSP), including its clinical manifestations, etiology, diagnosis, and treatment methods. Although modern medical interventions have helped, there is still room for improvement in the treatment of this disorder.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Claudia Dosi, Rosa Pasquariello, Chiara Ticci, Guja Astrea, Rosanna Trovato, Anna Rubegni, Alessandra Tessa, Giovanni Cioni, Filippo Maria Santorelli, Roberta Battini
Summary: HSPs are a genetically and clinically diverse group of neurodegenerative disorders characterized by progressive spasticity of the lower limbs. MRI can help in excluding mimicking disorders and guiding genetic testing.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
Domitilla Russo, Francesco Cappelli, Gianluca Di Bella, Giacomo Tini, Aldostefano Porcari, Alberto Cipriani, Marco Canepa, Marco Merlo, Roberto Licordari, Pier Filippo Vianello, Mattia Zampieri, Laura De Michieli, Riccardo Scirpa, Federico Perfetto, Gianfranco Sinagra, Camillo Autore, Claudio Rapezzi, Maria Beatrice Musumeci
Summary: This study analyzed the electrocardiographic characteristics of patients with vATTR and their correlation with clinical and echocardiographic aspects, focusing on different TTR mutations. The results showed that different TTR mutations tend to have distinctive ECG features and are associated with distinct instrumental and clinical features.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2023)
Review
Pathology
Grainne Mulkerrin, Marcondes C. Franca, Jasmin Lope, Ee Ling Tan, Peter Bede
Summary: This article reviews the progress of imaging techniques in hereditary spastic paraplegias (HSP). The study highlights the use of various imaging modalities, study design, clinical correlations, and methodological approaches in HSP cohorts. Current limitations include genetically admixed cohorts, small sample sizes, lack of postmortem validation, and limited clinical battery. However, collaborative multicenter initiatives and comprehensive clinical profiling have the potential to overcome these limitations and develop viable clinical applications for HSP imaging.
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2022)
Article
Clinical Neurology
Sebastian Viertauer, Ingo Kurth, Katja Eggermann, Christian Eggers
Summary: This study describes a family with hereditary spastic paraplegia and a unique cerebellar oculomotor dysfunction. Genetic analysis identified two previously unknown mutations of the PNPLA6 gene. Treatment with a potassium channel blocker resulted in meaningful improvement of clinical symptoms.
JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
Diana Maria Cubillos Arcila, Gustavo Dariva Machado, Valeria Feijo Martins, Vanessa Bielefeldt Leotti, Rebecca Schuele, Leonardo Alexandre Peyre-Tartaruga, Jonas Alex Morales Saute
Summary: The study found that both performance and clinician-reported outcomes can capture long-term progression of HSPs, with some gait performance outcomes showing greater sensitivity to change. The data presented are crucial for planning future therapeutic trials for this currently untreatable group of diseases.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Clinical Neurology
Wotu Tian, Haoran Zheng, Zeyu Zhu, Chao Zhang, Xinghua Luan, Li Cao
Summary: In this study, we described the clinical and genetic features of three SPG12 patients, identified three novel RTN2 mutations, and explored their potential pathogenic mechanisms. Our findings revealed the expanding RTN2-related spectrum and highlighted the phenotypic heterogeneity of SPG12.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Clinical Neurology
Ibrahim Sahin, Hanife Saat
Summary: This study identified 22 specific HSPs-HSAs-SAP mutations, including 14 novel mutations, in 25 patients with spastic or spastic-ataxic gait, expanding the clinical and molecular scope of HSP and clarifying the concept of the spasticity-ataxia phenotype. The research reveals a robust genotype-phenotype heterogeneity in the disease, broadening the spectrum of HSPs and HSAs related gene mutations and providing insights for genotype-phenotype correlations for HSPs and HSAs.
ACTA NEUROLOGICA BELGICA
(2022)
Review
Biochemistry & Molecular Biology
Liena E. O. Elsayed, Isra Zuhair Eltazi, Ammar E. Ahmed, Giovanni Stevanin
Summary: Hereditary spastic paraplegias (HSP) are a heterogeneous group of motor neurodegenerative disorders characterized by a variety of clinical manifestations and modes of inheritance, posing challenges in diagnosis. Understanding the genetic and molecular pathways of HSP is crucial for the development of future biomarkers, predictors, and treatments.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Neurosciences
Gautam Wali, Sue-Faye Siow, Erandhi Liyanage, Kishore R. R. Kumar, Alan Mackay-Sim, Carolyn M. M. Sue
Summary: HSP-SPAST is the most common form of hereditary spastic paraplegia (HSP), causing lower limb spasticity. Both patient-derived cortical neurons and peripheral blood mononuclear cells (PBMCs) show reduced levels of acetylated alpha-tubulin, which can be restored by noscapine treatment. Noscapine treatment can potentially benefit HSP-SPAST patients by increasing acetylated alpha-tubulin levels.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Neurosciences
Qiao Wei, Hao Yu, Pei-Shan Wang, Juan-Juan Xie, Hai-Lin Dong, Zhi-Ying Wu, Hong-Fu Li
Summary: This study identified five different COQ4 variants in three Chinese HSP pedigrees, expanding the phenotypic spectrum of COQ4-related disorders. Additionally, two early-onset pure HSP cases caused by COQ4 variants were described for the first time.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Neurosciences
Yongping Chen, Gopinath Krishnan, Sepideh Parsi, Marine Pons, Veroniki Nikolaki, Lu Cao, Zuoshang Xu, Fen-Biao Gao
Summary: The enhanced association between mutant CHMP2B and spastin may represent a novel pathological link between FTD3 and HSP. This association could contribute to the development of FTD3 and HSP.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Clinical Neurology
Nathalie De Beukelaer, Lynn Bar-On, Britta Hanssen, Nicky Peeters, Sandra Prinsen, Els Ortibus, Kaat Desloovere, Anja Van Campenhout
Summary: Hereditary spastic paraplegia (HSP) is a neurological, genetic disorder characterized by lower limb spasticity and muscle weakness, similar to children with bilateral spastic cerebral palsy (SCP). Muscle data analysis revealed significant ankle clonus issues in children with HSP.
FRONTIERS IN NEUROLOGY
(2021)
Article
Clinical Neurology
Ashraf Yahia, Zhefan Stephen Chen, Ammar E. Ahmed, Sara Emad, Rawaa Adil, Rayan Abubaker, Shaimaa Omer M. A. Taha, Mustafa A. Salih, Liena Elsayed, Ho Yin Edwin Chan, Giovanni Stevanin
Summary: A 48-year-old Sudanese female presented with early-onset hereditary spastic paraplegia, with genetic testing suggesting a potential association with variants in the CCDC88C gene, further experiments showed that the variant induced enhanced apoptosis. In contrast to previous studies, the patient manifested early neurological symptoms without other characteristic features.
Letter
Clinical Neurology
Marianthi Breza, Jennifer Hirst, Viorica Chelban, Guillaume Banneau, Laurene Tissier, Bophara Kol, Thomas Bourinaris, Samia A. Said, Yann Pereon, Anna Heinzmann, Rabab Debs, Raul Juntas-Morales, Victoria G. Martinez, Jean P. Camdessanche, Clarisse Scherer-Gagou, Jean-Medard Zola, Alkyoni Athanasiou-Fragkouli, Stephanie Efthymiou, George Vavougios, Georgios Velonakis, Maria Stamelou, John Tzartos, Constantin Potagas, Thomas Zambelis, Caterina Mariotti, Craig Blackstone, Jana Vandrovcova, Theodoros Mavridis, Chrisoula Kartanou, Leonidas Stefanis, Nicholas Wood, Georgia Karadima, Eric LeGuern, Georgios Koutsis, Henry Houlden, Giovanni Stevanin
MOVEMENT DISORDERS
(2021)
Article
Genetics & Heredity
Mutaz Amin, Cedric Vignal, Ahlam A. A. Hamed, Inaam N. Mohammed, Maha A. Elseed, Severine Drunat, Arwa Babai, Esraa Eltaraifee, Iman Elbadi, Rayan Abubaker, Doaa Mustafa, Ashraf Yahia, Mahmoud Koko, Melka Osman, Yousuf Bakhit, Azza Elshafea, Mohamed Alsiddig, Sahwah Haroun, Gurvan Lelay, Liena E. O. Elsayed, Ammar E. Ahmed, Odile Boespflug-Tanguy, Imen Dorboz
Summary: Mutations in the MLC1 gene were identified in leukodystrophic patients from Sudan, with a high frequency of deleterious variants compared to other populations. The inheritance pattern was autosomal recessive, with clinical presentation and brain MRI consistent with MLC1 diagnosis.
JOURNAL OF HUMAN GENETICS
(2022)
Article
Clinical Neurology
Ashraf Yahia, Liena E. O. Elsayed, Remi Valter, Ahlam A. A. Hamed, Inaam N. Mohammed, Maha A. Elseed, Mustafa A. Salih, Typhaine Esteves, Nicolas Auger, Rayan Abubaker, Mahmoud Koko, Fatima Abozar, Hiba Malik, Rawaa Adil, Sara Emad, Mhammed Alhassan Musallam, Razaz Idris, Isra Z. M. Eltazi, Arwa Babai, Elhami A. A. Ahmed, Amal S. Abd Allah, Mathilde Mairey, Ahmed K. M. A. Ahmed, Mustafa Elbashir, Alexis Brice, Muntaser E. Ibrahim, Ammar E. Ahmed, Foudil Lamari, Giovanni Stevanin
Summary: This study aimed to identify disease-causing variants in Sudanese families with a neurological phenotype, finding that homozygous variants in ABHD16A were associated with a novel form of complex hereditary spastic paraplegia.
FRONTIERS IN NEUROLOGY
(2021)
Article
Genetics & Heredity
Ashraf Yahia, Ikhlas Ben Ayed, Ahlam A. Hamed, Inaam N. Mohammed, Maha A. Elseed, Aisha M. Bakhiet, Lena Guillot-Noel, Fatima Abozar, Rawaa Adil, Sara Emad, Rayan Abubaker, Mhammed Alhassan Musallam, Isra Z. M. Eltazi, Zulfa Omer, Omer M. Maaroof, Amal Soussi, Amal Bouzid, Sana Kmiha, Hassen Kamoun, Mustafa A. Salih, Ammar E. Ahmed, Liena Elsayed, Saber Masmoudi, Giovanni Stevanin
Summary: In this study, pathogenic mutations in the genes CCDC82, ADAT3, and HUWE1 were identified in patients with syndromic intellectual disability. The CCDC82-linked phenotype may include spastic paraplegia and microcephaly, expanding the understanding of this genetic disorder.
ANNALS OF HUMAN GENETICS
(2022)
Article
Clinical Neurology
Marie Coutelier, Maxime Jacoupy, Alexandre Janer, Flore Renaud, Nicolas Auger, Ganapathi-Varma Saripella, Francois Ancien, Fabrizio Pucci, Marianne Rooman, Dimitri Gilis, Roxanne Lariviere, Nicolas Sgarioto, Remi Valter, Lena Guillot-Noel, Isabelle Le Ber, Sabrina Sayah, Perrine Charles, Astrid Nuemann, Martje G. Pauly, Christoph Helmchen, Natalie Deininger, Tobias B. Haack, Bernard Brais, Alexis Brice, David-Alexandre Tregouet, Khalid H. El Hachimi, Eric A. Shoubridge, Alexandra Durr, Giovanni Stevanin
Summary: With exome sequencing and linkage analysis, we identified an association between NPTX1 gene and autosomal dominant cerebellar ataxias. Two missense variants in NPTX1 were found to induce endoplasmic reticulum stress and destabilize neuronal pentraxin 1 polymers.
Article
Clinical Neurology
Jean-Loup Mereaux, Guillaume Banneau, Melanie Papin, Giulia Coarelli, Remi Valter, Laure Raymond, Bophara Kol, Olivier Ariste, Livia Parodi, Laurene Tissier, Mathilde Mairey, Samia Ait Said, Celia Gautier, Marine Guillaud-Bataille, Sylvie Forlani, Pierre de la Grange, Alexis Brice, Giovanni Vazza, Alexandra Durr, Eric Leguern, Giovanni Stevanin
Summary: This study reports the clinical and genetic results of a large cohort of patients with hereditary spastic paraplegia. A causative variant was found in 30.7% of the patients, with SPAST and SPG7 being the most frequently mutated genes. A two-step strategy combining gene panels and whole-exome sequencing is proposed to improve the diagnostic yield.
Article
Clinical Neurology
Liedewei Van de Vondel, Jonathan De Winter, Danique Beijer, Giulia Coarelli, Melanie Wayand, Robin Palvadeau, Martje G. Pauly, Katrin Klein, Maren Rautenberg, Lena Guillot-Noel, Tine Deconinck, Atay Vural, Sibel Ertan, Okan Dogu, Hilmi Uysal, Vesna Brankovic, Rebecca Herzog, Alexis Brice, Alexandra Durr, Stephan Klebe, Friedrich Stock, Almut Turid Bischoff, Tim W. Rattay, Maria-Jesus Sobrido, Giovanna De Michele, Peter De Jonghe, Thomas Klopstock, Katja Lohmann, Ginevra Zanni, Filippo M. Santorelli, Vincent Timmerman, Tobias B. Haack, Stephan Zuchner, Rebecca Schuele, Giovanni Stevanin, Matthis Synofzik, A. Nazli Basak, Jonathan Baets
Summary: This study identifies the association between SPTAN1 gene and neurological disorders such as ataxia and spastic paraplegia. Through screening a large number of datasets and protein modeling, multiple SPTAN1 variants are identified, and disrupted interlinking of spectrin helices is suggested as a key feature of the pathomechanism.
MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
Maha Dahawi, Mohamed S. Elmagzoub, Elhami A. Ahmed, Sara Baldassari, Guillaume Achaz, Fatima A. Elmugadam, Wasma A. Abdelgadir, Stephanie Baulac, Julien Buratti, Omer Abdalla, Sahar Gamil, Maha Alzubeir, Rayan Abubaker, Eric Noe, Liena Elsayed, Ammar E. Ahmed, Eric Leguern
Summary: This study identified novel ADGRV1 gene variants associated with GGE in a Sudanese population, indicating that this gene is a susceptibility gene for CAE/JEA and GGE-TCS phenotypes. Genotype-phenotype correlations in affected families revealed a significant association between ADGRV1 variants and GGE phenotypes.
FRONTIERS IN NEUROLOGY
(2021)
Article
Genetics & Heredity
Mutaz Amin, Cedric Vignal, Ahlam A. A. Hamed, Inaam N. Mohammed, Maha A. Elseed, Rayan Abubaker, Yousuf Bakhit, Arwa Babai, Eman Elbadi, Esraa Eltaraifee, Doua Mustafa, Ashraf Yahia, Melka Osman, Mahmoud Koko, Mohamed Mustafa, Mohamed Alsiddig, Sahwah Haroun, Azza Elshafea, Severine Drunat, Liena E. O. Elsayed, Ammar E. Ahmed, Odile Boespflug-Tanguy, Imen Dorboz
Summary: Pontocerebellar hypoplasia type 10 (PCH10) is a rare neurodegenerative disease characterized by intellectual disability, microcephaly, and developmental delay. It is caused by a founder missense pathogenic variant in the CLP1 gene. This study identified cases of PCH10 in a non-Turkish family for the first time, highlighting the phenotypic expansion of the disease.
FRONTIERS IN GENETICS
(2022)
Article
Clinical Neurology
Yousuf Bakhit, Ina Schmitt, Ahlam Hamed, Etedal Ahmed A. Ibrahim, Inaam N. Mohamed, Sarah M. El-Sadig, Maha A. Elseed, Mohamed A. Alebeed, Mutaz T. Shaheen, Mohamed O. Ibrahim, Ali A. Elhassan, Khalid Eltom, Hiba A. Ali, Yousuf A. Ibrahim, Murad E. Almak, Rayan Abubaker, Mohamed Anwer Ahmed, Ahmed A. Abugrain, Salma M. Elrasheed, Mawia A. Omar, Mohamed A. Almahal, Abubaker A. MohamedSharif, Mohamed Y. Tahir, Sawazen M. Malik, Hazim S. Eldirdiri, Reem J. Khidir, Malaz T. Mohamed, Abdelmohaymin Abdalla, Farouk Yassen Omer, Liena E. O. Elsayed, Haydar El Hadi Babikir, Elfateh Abd-Allah Bukhari, Osheik Seidi, Ullrich Wuellner
Summary: After studying several Parkinson's disease patients in Sudan, the team discovered a specific pattern of DNA methylation that plays a crucial role in the occurrence of familial Parkinson's disease.
PARKINSONISM & RELATED DISORDERS
(2022)
Article
Genetics & Heredity
Mutaz Amin, Cedric Vignal, Esraa Eltaraifee, Inaam N. Mohammed, Ahlam A. A. Hamed, Maha A. Elseed, Arwa Babai, Iman Elbadi, Doua Mustafa, Rayan Abubaker, Mohamed Mustafa, Severine Drunat, Liena E. O. Elsayed, Ammar E. Ahmed, Odile Boespflug-Tanguy, Imen Dorboz
Summary: This study reports two siblings with intellectual disabilities from Sudan who carry a novel mutation in the TRAPPC9 gene. This is the first report of TRAPPC9-related disorder patients from Sub-Saharan Africa.
BMC MEDICAL GENOMICS
(2022)
Article
Genetics & Heredity
Sandra Martins, Ashraf Yahia, Ines P. D. Costa, Hassab E. Siddig, Rayan Abubaker, Mahmoud Koko, Marc Corral-Juan, Antoni Matilla-Duenas, Alexis Brice, Alexandra Durr, Eric Leguern, Laura P. W. Ranum, Antonio Amorim, Liena E. O. Elsayed, Giovanni Stevanin, Jorge Sequeiros
Summary: Machado-Joseph disease (MJD/SCA3) is the most common dominant ataxia worldwide, caused by a (CAG)n expansion. This study reports the first diagnosed MJD case in Sudan, with genetic analysis revealing shared ancestry with Portuguese, Spanish, and North American families. The STR-based haplotype of the Sudanese patients is distinct, indicating a unique genetic background.
Meeting Abstract
Biochemistry & Molecular Biology
Liena E. O. Elsayed, Inaam N. Mohammed, Ahlam A. A. Hamed, Maha A. Elseed, Arwa M. A. Babai, Elhami A. A. Ahmed, Doua M. S. AbdelGaleel, Isra Z. M. Eltazi, Rayan A. Siddig, Esraa E. Eltaraife, Amal S. I. Abd Allah, Atheer Eltigani, Nabila M. H. Ali, Sarah M. El-Sadig, Afraa M. M. Musa, Mahmoud E. Koko, Ashraf Y. O. Mohamed, Mustafa I. Elbashir, Alexis Brice, Giovanni Stevanin, Ammar E. Ahmed, Muntaser E. Ibrahim
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)