Review
Clinical Neurology
Arianna Ferrini, Dora Steel, Katy Barwick, Manju A. Kurian
Summary: ADCY5-related disease encompasses a range of hyperkinetic disorders with the causative gene encoding adenylyl cyclase. cAMP serves as a second messenger exerting various effects through multiple signaling pathways. Currently, there are no disease-modifying treatments available.
MOVEMENT DISORDERS
(2021)
Article
Multidisciplinary Sciences
Dirk Taenzler, Marc Kipping, Marcell Lederer, Wiebke Guenther, Christian Arlt, Stefan Huettelmaier, Andreas Merkenschlager, Andrea Sinz
Summary: We demonstrated the effects of caffeine, theophylline, and istradefylline on cAMP production by ADCY5-overexpressing cell lines. cAMP levels were compared between ADCY5 wild-type and R418W mutant cells. The purine derivatives reduced ADCY5-catalyzed cAMP production, with the R418W mutant cells showing the most significant reduction. In a case study, a slow-release formulation of theophylline showed better improvement in symptoms of ADCY5-related dyskinesia compared to previously administered caffeine. Theophylline could be considered as an alternative therapeutic option for treating ADCY5-related dyskinesia in patients.
Article
Clinical Neurology
Aurelie Meneret, Shekeeb S. Mohammad, Laura Cif, Diane Doummar, Claudio DeGusmao, Mathieu Anheim, Magalie Barth, Philippe Damier, Nathalie Demonceau, Jennifer Friedman, Cecile Gallea, Domitille Gras, Juliana Gurgel-Giannetti, Emily A. Innes, Jan Necpal, Florence Riant, Sandrine Sagnes, Catherine Sarret, Yury Seliverstov, Vijayashankar Paramanandam, Kuldeep Shetty, Christine Tranchant, Mohamed Doulazmi, Marie Vidailhet, Tamara Pringsheim, Emmanuel Roze
Summary: A retrospective study found that caffeine is effective in improving symptoms of ADCY5-related dyskinesia and should be considered as a first-line treatment option with good tolerability.
MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
Audrey Pontrucher, Magalie Barth, Alban Ziegler, Juan Manuel Chao de la Barca, Delphine Mirebeau-Prunier, Pascal Reynier, Chadi Homedan
Summary: This article reports the misleading superposition of two inherited metabolic diseases, showing the importance of clinical-biological confrontation in the interpretation of genetic variants.
FRONTIERS IN NEUROLOGY
(2023)
Review
Neurosciences
Miriam Kessi, Baiyu Chen, Nan Pang, Lifen Yang, Jing Peng, Fang He, Fei Yin
Summary: Genotype-phenotype correlations and potential treatment for CACNA1A-related neurodevelopmental disorders were summarized in this study. It was found that the p.A713T variant is associated with severe-profound GDD/ID, and more than half of CACNA1A-related epilepsy is refractory.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Clinical Neurology
Jingru Ren, Ronggui Zhang, Chenxi Pan, Jianxia Xu, Haochen Sun, Ping Hua, Li Zhang, Wenbin Zhang, Pingyi Xu, Changyan Ma, Weiguo Liu
Summary: This study aimed to determine the frequency of GBA-related PD and the relationship between GBA variant severity and clinical characteristics in a large Chinese cohort. The results showed that GBA-PD is highly prevalent in the Chinese population, and patients carrying severe and complex variants have more severe symptoms.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Review
Genetics & Heredity
Ze-Xu Chen, Wan-Nan Jia, Yong-Xiang Jiang
Summary: Marfan syndrome is a heritable multisystemic disease with a wide range of clinical manifestations. Understanding the genotype-phenotype correlations can provide valuable information for risk assessment, prognosis, and treatment selection.
FRONTIERS IN GENETICS
(2022)
Article
Clinical Neurology
Xiuli Huang, Dandan Tan, Zaiqiang Zhang, Lin Ge, Jieyu Liu, Juan Ding, Haipo Yang, Cuijie Wei, Xingzhi Chang, Yun Yuan, Chuanzhu Yan, Hui Xiong
Summary: This study conducted a retrospective cross-sectional and longitudinal study on 19 Chinese patients with LAMA2-related limb girdle muscular dystrophy (LGMD R23), and found that most patients had normal early motor development, some had mild orthopedic complications, 36.8% had seizures, and 26.3% were diagnosed with epilepsy. Genetic analysis identified 29 pathogenic variants, with missense and frameshift variants being the most common. Missense variants in exon 4 may be correlated with epilepsy, and variants in the LN domain may be correlated with motor neuropathy. The study expands the clinical and genetic spectrum caused by LAMA2 variations and provides novel genotype-phenotype correlations of LGMD R23.
FRONTIERS IN NEUROLOGY
(2023)
Article
Medicine, Research & Experimental
T. A. Meridian McDonald
Summary: The paper discusses the increase in autism prevalence over the last 60 years with an unclear cause, proposing explanatory paradigms for autism and its increased prevalence in the general population. It introduces the concept of Broader Autism Phenotype Constellations (BAPCO) and suggests that assortative mating opportunities may have contributed to the increased frequency of these traits. The paper also introduces the BAPCO-Disability Matrix Paradigm (BAPCO-DMAP) to redefine autism in a way that includes constellations of BAPCO traits and co-occurring conditions.
MEDICAL HYPOTHESES
(2021)
Review
Biochemistry & Molecular Biology
Steven K. Brennan, Thomas W. Ferkol, Stephanie D. Davis
Summary: PCD is a rare inherited condition affecting motile cilia and leading to organ laterality defects, recurrent infections, bronchiectasis, and severe lung disease. Research has shown variability in clinical presentations and relationships between genotype and phenotype. Advancements in genetic testing continue to redefine these relationships and uncover previously unrecognized milder forms of the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Filomena Napolitano, Milena Dell'Aquila, Chiara Terracciano, Giuseppina Franzese, Maria Teresa Gentile, Giulio Piluso, Claudia Santoro, Davide Colavito, Anna Patane, Paolo De Blasiis, Simone Sampaolo, Simona Paladino, Mariarosa Anna Beatrice Melone
Summary: The study aimed to investigate the molecular spectrum and genotype-phenotype correlations of NF1, finding that the majority of patients exhibited a severe phenotype with various complications and associated malignancies. Patients carrying frameshift mutations showed a higher prevalence of learning disabilities.
Review
Clinical Neurology
Poornima Jayadev Menon, Christelle Nilles, Laura Silveira-Moriyama, Ruiyi Yuan, Claudio M. de Gusmao, Alexander Muenchau, Miryam Carecchio, Steve Grossman, Gay Grossman, Aurelie Meneret, Emmanuel Roze, Tamara Pringsheim
Summary: This scoping review summarizes the available clinical literature on ADCY5-RMD. Patients with ADCY5-RMD experience permanent and/or paroxysmal hyperkinetic movements, which can be worsened by environmental triggers. Treatment options are limited, but caffeine, benzodiazepines, and deep brain stimulation have shown some effectiveness.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Genetics & Heredity
Xudong Wang, Zhongmin Xia, Ying He, Xiaoman Zhou, Haixia Zhang, Chunliu Gao, Yunsheng Ge, Xiaofang Cai, Yulin Zhou, Qiwei Guo
Summary: This study evaluated the profile of G6PD deficiency in Xiamen, China, finding a prevalence of 1.39% and identifying 12 variants and 32 genotypes, with the six most common variants accounting for approximately 94% of the identified alleles. The use of genotyping helped confirm the presence of pathogenic G6PD variants and improve the accuracy of newborn screening, with cold-chain transportation significantly enhancing the positive predictive value (PPV).
FRONTIERS IN GENETICS
(2021)
Article
Clinical Neurology
Didem Tezen, Aysegul Gunduz, Meral Erdemir Kiziltan, Cengiz Yalcinkaya, Gunes Kiziltan
Summary: This report examines the case of a 5-year-old girl with early onset involuntary movements. The patient was found to have an ADCY5 gene mutation through whole exome sequencing. The study aims to contribute to a better understanding of the gene and the discovery of different treatment options.
NEUROLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Bin Li, Zheng Wang, Qian Chen, Kuokuo Li, Xiaomeng Wang, Yijing Wang, Qian Zeng, Ying Han, Bin Lu, Yuwen Zhao, Rui Zhang, Li Jiang, Hongxu Pan, Tengfei Luo, Yi Zhang, Zhenghuan Fang, Xuewen Xiao, Xun Zhou, Rui Wang, Lu Zhou, Yige Wang, Zhenhua Yuan, Lu Xia, Jifeng Guo, Beisha Tang, Kun Xia, Guihu Zhao, Jinchen Li
Summary: To address the challenge of accessing detailed clinical phenotypic features of patients with genetic variants, researchers developed an online database called GPCards, which integrates genetic and clinical data to provide interpretation of genotype-phenotype correlations and prioritization of candidate functional variants. This tool accelerates the interpretation of genotype-phenotype correlations in human genetic diseases and aids researchers in making faster diagnostic and treatment decisions.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Clinical Neurology
Marie Stoessel, Francois Lersy, Mylene Moris, Guillaume Bierry, Mathieu Anheim, Stephane Kremer, Sabrina Garnier-Kepka
Summary: This study evaluated the implementation of a dedicated MRI scanner for the management of patients with binocular diplopia in the emergency department. The results showed that the use of the MRI scanner improved the diagnostic performance of binocular diplopia and reduced patient's exposure to ionizing radiation without increasing turnaround time or emergency department length of stay.
JOURNAL OF NEURORADIOLOGY
(2023)
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
Amjad Khan, Anne Molitor, Sylvain Mayeur, Gaoqun Zhang, Bruno Rinaldi, Beatrice Lannes, Benoit Lhermitte, Muhammad Umair, Stefan T. Arold, Sylvie Friant, Sepand Rastegar, Mathieu Anheim, Seiamak Bahram, Raphael Carapito
Summary: A novel missense variant in the PPP1R1B gene was identified in a consanguineous family with generalized dystonia. The expression of PPP1R1B protein in movement control regions suggests its involvement in abnormal movements, making it a potential gene to be sequenced in patients with unexplained movement disorders.
MOVEMENT DISORDERS
(2022)
Editorial Material
Clinical Neurology
Thomas Wirth, Izzie Jacques Namer, Ben Monga, Caroline Bund, Andra Valentina Iosif, Odile Gebus, Solveig Montaut, Thomas Bogdan, Laura Robelin, Mathilde Renaud, Stephane Kremer, Christine Tranchant, Mathieu Anheim
Summary: This study aimed to investigate the progression of nigrostriatal dopaminergic denervation (NSDD) in cerebellar multiple system atrophy (MSA-C) and evaluate its differentiation from idiopathic late-onset cerebellar ataxia (ILOCA). The results showed that rapid symptom worsening and NSDD existence and progression could predict the occurrence of MSA-C.
Article
Clinical Neurology
Aurelie Meneret, Shekeeb S. Mohammad, Laura Cif, Diane Doummar, Claudio DeGusmao, Mathieu Anheim, Magalie Barth, Philippe Damier, Nathalie Demonceau, Jennifer Friedman, Cecile Gallea, Domitille Gras, Juliana Gurgel-Giannetti, Emily A. Innes, Jan Necpal, Florence Riant, Sandrine Sagnes, Catherine Sarret, Yury Seliverstov, Vijayashankar Paramanandam, Kuldeep Shetty, Christine Tranchant, Mohamed Doulazmi, Marie Vidailhet, Tamara Pringsheim, Emmanuel Roze
Summary: A retrospective study found that caffeine is effective in improving symptoms of ADCY5-related dyskinesia and should be considered as a first-line treatment option with good tolerability.
MOVEMENT DISORDERS
(2022)
Letter
Clinical Neurology
Thomas Wirth, Aurelie Meneret, Nathalie Drouot, Gabrielle Rudolf, Ouhaid Lagha Boukbiza, Jamel Chelly, Christine Tranchant, Amelie Piton, Emmanuel Roze, Mathieu Anheim
MOVEMENT DISORDERS
(2022)
Article
Chemistry, Analytical
David Amarantini, Isabelle Rieu, Giovanni Castelnovo, Frederique Fluchere, Chloe Laurencin, Bertrand Degos, Aurelia Poujois, Alexandre Kreisler, Sophie Sangla, Melissa Tir, Isabelle Benatru, Genevieve Blanchet-Fourcade, Dominique Guehl, Dominique Gayraud, Laurent Tatu, Christine Tranchant, Franck Durif, Marion Simonetta-Moreau
Summary: This study compares two methods, video-based motion analysis and miniature wireless inertial magnetic motion unit (IMMU), to quantify the amplitude and frequency of head movements in patients with head tremor. The results show that the IMMU method is more sensitive in detecting changes in tremor amplitude and has better agreement with clinical measures.
Article
Genetics & Heredity
Jason Hulen, Dorothy Kenny, Rebecca Black, Jodi Hallgren, Kelley G. Hammond, Eric C. Bredahl, Rochelle N. Wickramasekara, Peter W. Abel, Holly A. F. Stessman
Summary: Disruptive variants in the KMT5B/SUV4-20H1 gene have been found to be likely-pathogenic in humans with neurodevelopmental phenotypes, including motor deficits. However, the role of this enzyme in early motor development is currently unknown. Using a mouse model, researchers have found that Kmt5b gene deficiency leads to skeletal muscle developmental deficits, including reduced muscle mass and body weight.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Hadley Stevens Smith, Emily S. Bonkowski, Raymond Belanger Deloge, Amanda M. Gutierrez, Alva M. Recinos, Tara A. Lavelle, David L. Veenstra, Amy L. McGuire, Stacey Pereira
Summary: This study explores the key considerations for caregivers of pediatric patients regarding clinical genomic sequencing, with a focus on family-level considerations. The findings reveal that caregivers not only consider their child's well-being, but also take into account the impact on family quality of life, knowledge about family health, the caregiver's own well-being, privacy concerns among family members, and the cost of testing. A framework of key drivers of utility for decision making in clinical genomic sequencing is proposed, including underlying values, perceived benefits, perceived risks, and other pragmatic considerations.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Letter
Clinical Neurology
Serdar Kazanci, Jennifer Witt, Kimmy Su, Oswaldo Lorenzo-Betancor, Dora Yearout, Cyrus P. Zabetian, Marie Y. Davis
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Editorial Material
Ethics
Emily Bonkowski, Hadley Stevens Smith
AMERICAN JOURNAL OF BIOETHICS
(2023)
Article
Genetics & Heredity
Oriane Trouillard, Pauline Dupaigne, Margaux Dunoyer, Mohamed Doulazmi, Morten Krogh Herlin, Solene Frismand, Audrey Riou, Veronique Legros, Guillaume Chevreux, Xavier Veaute, Didier Busso, Coralie Fouquet, Cecile Saint-Martin, Aurelie Meneret, Alain Trembleau, Isabelle Dusart, Caroline Dubacq, Emmanuel Roze
Summary: Mirror movements are involuntary movements of one hand that mirror intentional movements of the other hand. Congenital mirror movements (CMM) is a rare genetic disorder with autosomal dominant inheritance, in which mirror movements are the main neurological manifestation. RAD51 haploinsufficiency, including loss-of-function of non-truncating variants, results in CMM.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Pediatrics
Hadley Stevens Smith, Emily S. Bonkowski, Madison R. Hickingbotham, Raymond Belanger Deloge, Stacey Pereira
Summary: Families of children with rare and undiagnosed conditions face challenges that affect their decision-making about their child's care. Understanding the family-level characteristics that shape the experience of genomic sequencing (GS) is crucial. Interviews with parents of pediatric patients undergoing or completed GS revealed three domains of factors that influence the family-level experience: family structure and dynamics, parental identity and relationships, and social and cultural differences. These findings can inform preference research and genetic counseling.
Review
Clinical Neurology
Poornima Jayadev Menon, Christelle Nilles, Laura Silveira-Moriyama, Ruiyi Yuan, Claudio M. de Gusmao, Alexander Muenchau, Miryam Carecchio, Steve Grossman, Gay Grossman, Aurelie Meneret, Emmanuel Roze, Tamara Pringsheim
Summary: This scoping review summarizes the available clinical literature on ADCY5-RMD. Patients with ADCY5-RMD experience permanent and/or paroxysmal hyperkinetic movements, which can be worsened by environmental triggers. Treatment options are limited, but caffeine, benzodiazepines, and deep brain stimulation have shown some effectiveness.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Asya Ekmen, Mohamed Doulazmi, Aurelie Meneret, Prasanthi Jegatheesan, Anais Herve, Philippe Damier, Domitille Gras, Agathe Roubertie, Juliette Piard, Eugenie Mutez, Clement Tarrano, Quentin Welniarz, Marie Vidailhet, Yulia Worbe, Cecile Gallea, Emmanuel Roze
Summary: This study investigated the relationship between non-motor symptoms and health-related quality of life (HrQoL) in PKD patients caused by monoallelic pathogenic variants of PRRT2. The study found that non-motor manifestations were an important determinant of HrQoL and patients also experienced higher levels of self-esteem and stigmatization. The results have important implications for patient management and medical education about PKD.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)