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Diagnosis of Neurogenetic Disorders Contribution of Next Generation Sequencing and Deep Phenotyping brain sciences Diagnosis of Neurogenetic Disorders Contribution of Next Generation Sequencing and Deep Phenotyping Edited by Alisdair McNeill Printed Edition of the Special Issue Published in Brain Sciences www.mdpi.com/journal/brainsci Diagnosis of Neurogenetic Disorders Diagnosis of Neurogenetic Disorders: Contribution of Next Generation Sequencing and Deep Phenotyping Special Issue Editor Alisdair McNeill MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade Special Issue Editor Alisdair McNeill University of Sheffield UK Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal Brain Sciences (ISSN 2076-3425) from 2018 to 2019 (available at: https://www.mdpi.com/journal/ brainsci/special issues/diagnosis neurogenetic disorders) For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year, Article Number, Page Range. ISBN 978-3-03921-610-9 (Pbk) ISBN 978-3-03921-611-6 (PDF) c 2019 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND. Contents About the Special Issue Editor ...................................... vii Alisdair McNeill Editorial for Brain Sciences Special Issue: “Diagnosis of Neurogenetic Disorders: Contribution of Next-Generation Sequencing and Deep Phenotyping” Reprinted from: Brain Sci. 2019, 9, 72, doi:10.3390/brainsci9030072 .................. 1 Jennifer F. Gardner, Thomas D. Cushion, Georgios Niotakis, Heather E. Olson, P. Ellen Grant, Richard H. Scott, Neil Stoodley, Julie S. Cohen, Sakkubai Naidu, Tania Attie-Bitach, Maryse Bonni`eres, Lucile Boutaud, F´erecht´e Encha-Razavi, Sheila M. Palmer-Smith, Hood Mugalaasi, Jonathan G. L. Mullins, Daniela T. Pilz and Andrew E. Fry Clinical and Functional Characterization of the Recurrent TUBA1A p.(Arg2His) Mutation Reprinted from: Brain Sci. 2018, 8, 145, doi:10.3390/brainsci8080145 ................. 3 Christopher Buckley, Lisa Alcock, R´ıonaMcArdle, Rana Zia Ur Rehman, Silvia Del Din, Claudia Mazz`a,Alison J. Yarnall and Lynn Rochester The Role of Movement Analysis in Diagnosing and Monitoring Neurodegenerative Conditions: Insights from Gait and Postural Control Reprinted from: Brain Sci. 2019, 9, 34, doi:10.3390/brainsci9020034 .................. 15 Emilia M. Gatto, Gustavo Da Prat, Jose Luis Etcheverry, Guillermo Drelichman and Martin Cesarini Parkinsonisms and Glucocerebrosidase Deficiency: A Comprehensive Review for Molecular and Cellular Mechanism of Glucocerebrosidase Deficiency Reprinted from: Brain Sci. 2019, 9, 30, doi:10.3390/brainsci9020030 .................. 36 Julio-C´esarGarc´ıaand Rosa-Helena Bustos The Genetic Diagnosis of Neurodegenerative Diseases and Therapeutic Perspectives Reprinted from: Brain Sci. 2018, 8, 222, doi:10.3390/brainsci8120222 ................. 51 Edward Botsford, Jayan George and Ellen E. Buckley Parkinson’s Disease and Metal Storage Disorders: A Systematic Review Reprinted from: Brain Sci. 2018, 8, 194, doi:10.3390/brainsci8110194 ................. 69 v About the Special Issue Editor Alisdair McNeill, Dr, received his MBChB (Hons) from Edinburgh University in 2004, and obtained his MRCP (UK) in 2007. He undertook Medical SHO training in Newcastle-upon-Tyne and Edinburgh, Clinical Genetics SpR training in the West Midlands, and an MRC Clinical Research Training Fellowship at UCL. His research interests are focused on the genetic causes of neurological disorders in both children and adults. McNeill is identifying new ways of phenotyping patients in order to improve diagnosis and disease monitoring, for example, through using patient-wearable movement sensors (collaboration with INSIGNEO) in adults with neurological disorders and 3-dimensional facial image analysis (collaboration with Prof Peter Hammond, Oxford) in children with chromosome microdeletions. He is also interested in studying variants of uncertain significance as identified in clinical genetics testing, and resolving their pathogenicity through clinical phenotyping and in vitro studies. vii brain sciences Editorial Editorial for Brain Sciences Special Issue: “Diagnosis of Neurogenetic Disorders: Contribution of Next-Generation Sequencing and Deep Phenotyping” Alisdair McNeill Department of Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield S10 2HQ, UK; a.mcneill@sheffield.ac.uk Received: 11 March 2019; Accepted: 19 March 2019; Published: 26 March 2019 In this Special Issue we bring together papers demonstrating the need for both detailed genomic and phenotypic studies to aid our scientific and clinical understanding of neurogenetic disorders. Genomic techniques such as genome and exome sequencing are vital tools for diagnosing rare neurogenetic disorders and identifying novel causal genes [1,2]. In this Special Issue, Gardner and colleagues [3] utilise genomic techniques to identify a series of individuals with brain malformations due to the recurrent TUBA1A p.Arg2His variant. This paper also describes the detailed phenotyping required to aid in the interpretation of novel genomic variants. Variants in GBA1, the gene causing Gaucher Disease (GD), are associated with an increased risk of Parkinson’s Disease (PD) [4,5]. Gatto and colleagues review this important area and describe how simple clinical observations helped begin the identification of this important risk factor for PD [6]. Genomic techniques are crucial for the diagnosis of neurogenetic disorders [7]. Garcia and Bustos [8] review the impact of such techniques for both the diagnosis of neurogenetic diseases and increasing our scientific understanding of these disorders. It is only through the co-development of both novel genomic and phenotypic assessments that we will be able to fully understand the pathogenesis of neurogenetic disorders and identify novel treatments. Conflicts of Interest: The author declares no conflict of interest. References 1. Hempel, A.; Pagnamenta, A.T.; Blyth, M.; Mansour, S.; McConnell, V.; Kou, I.; Ikegawa, S.; Tsurusaki, Y.; Matsumoto, N.; Lo-Castro, A.; et al. Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin-Siris syndrome. J. Med. Genet. 2016, 53, 152–162. [CrossRef][PubMed] 2. Blanchet, P.; Bebin, M.; Bruet, S.; Cooper, G.M.; Thompson, M.L.; Duban-Bedu, B.; Gerard, B.; Piton, A.; Suckno, S.; Deshpande, C.; et al. MYT1L mutations cause intellectual disability and variable obesity by dysregulating gene expression and development of the neuroendocrine hypothalamus. Plos Genet. 2017, 13, e1006957. [CrossRef][PubMed] 3. Gardner, J.F.; Cushion, T.D.; Niotakis, G.; Olson, H.E.; Grant, P.E.; Scott, R.H.; Stoodley, N.; Cohen, J.S.; Naidu, S.; Attie-Bitach, T.; Bonnières, M.; Boutaud, L.; Encha-Razavi, F.; Palmer-Smith, S.M.; Mugalaasi, H.; Mullins, J.G.L.; Pilz, D.T.; Fry, A.E. Clinical and Functional Characterization of the Recurrent TUBA1A p.(Arg2His) Mutation. Brain Sci. 2018, 8, 145. [CrossRef][PubMed] 4. McNeill, A.; Duran, R.; Proukakis, C.; Bras, J.; Hughes, D.; Mehta, A.; Hardy, J.; Wood, N.W.; Wood, A.H.V. Hyposmia and cognitive impairment in Gaucher disease patients and carriers. Mov. Disord. 2012, 27, 526–532. [CrossRef][PubMed] 5. McNeill, A.; Duran, R.; Hughes, D.A.; Mehta, A.; Schapira, A.H. A clinical and family history study of Parkinson’s disease in heterozygous glucocerebrosidase mutation carriers. J. Neurol. Neurosurg. Psych. 2012, 83, 853–854. [CrossRef][PubMed] Brain Sci. 2019, 9, 72; doi:10.3390/brainsci90300721 www.mdpi.com/journal/brainsci Brain Sci. 2019, 9,72 6. Gatto, E.M.; Da Prat, G.; Etcheverry, J.L.; Drelichman, G.; Cesarini, M. Parkinsonisms and Glucocerebrosidase Deficiency: A Comprehensive Review for Molecular and Cellular Mechanism of Glucocerebrosidase Deficiency. Brain Sci. 2019, 9, 30. [CrossRef][PubMed] 7. Majewski, J.; Schwartzentruber, J.; Lalonde, E.; Montpetit, A.; Jabado, N. What can exome sequencing do for you? J. Med. Genet. 2011, 48, 580–589. [CrossRef][PubMed] 8. García, J.-C.; Bustos, R.-H. The Genetic Diagnosis of Neurodegenerative Diseases and Therapeutic Perspectives. Brain Sci. 2018, 8, 222. [CrossRef][PubMed] © 2019 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). 2 brain sciences Article Clinical and Functional Characterization of the Recurrent TUBA1A p.(Arg2His) Mutation Jennifer F. Gardner 1,†, Thomas D. Cushion 2,†, Georgios Niotakis 3, Heather E. Olson 4, P. Ellen Grant 5, Richard H. Scott 6, Neil Stoodley 7, Julie S. Cohen 8, Sakkubai Naidu 8,9,10, Tania Attie-Bitach 11,12, Maryse Bonnières 11, Lucile Boutaud 11,12,Férechté Encha-Razavi 11, Sheila M. Palmer-Smith 1, Hood Mugalaasi 1, Jonathan G. L. Mullins 13, Daniela T. Pilz 2,14 and Andrew E. Fry 1,2,* 1 Institute of Medical Genetics, University Hospital of Wales, Cardiff CF14 4XW, UK; [email protected] (J.F.G.); [email protected] (S.M.P.-S.); [email protected]
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