Diagnosis of Neurogenetic Disorders: Contribution of Next Generation Sequencing and Deep Phenotyping

96 Pages·2019·6.976 MB·English

by  Alisdair McNeill (editor)

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
SpecialIssueEditor
AlisdairMcNeill
MDPI•Basel•Beijing•Wuhan•Barcelona•Belgrade
SpecialIssueEditor
AlisdairMcNeill
UniversityofSheffield
UK
EditorialOffice
MDPI
St.Alban-Anlage66
4052Basel,Switzerland
This is a reprint of articles from the Special Issue published online in the open access journal
BrainSciences (ISSN 2076-3425) from 2018 to 2019 (available at: https://www.mdpi.com/journal/
brainsci/specialissues/diagnosisneurogeneticdisorders)
Forcitationpurposes,citeeacharticleindependentlyasindicatedonthearticlepageonlineandas
indicatedbelow:
LastName,A.A.; LastName,B.B.; LastName,C.C.ArticleTitle. JournalNameYear,ArticleNumber,
PageRange.
ISBN978-3-03921-610-9(Pbk)
ISBN978-3-03921-611-6(PDF)
(cid:2)c 2019bytheauthors. ArticlesinthisbookareOpenAccessanddistributedundertheCreative
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disseminationandawiderimpactofourpublications.
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Contents
AbouttheSpecialIssueEditor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
AlisdairMcNeill
EditorialforBrainSciencesSpecialIssue: “DiagnosisofNeurogeneticDisorders: Contribution
ofNext-GenerationSequencingandDeepPhenotyping”
Reprintedfrom:BrainSci.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 Bonnie`res, Lucile Boutaud, Fe´rechte´ 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
Reprintedfrom:BrainSci.2018,8,145,doi:10.3390/brainsci8080145 . . . . . . . . . . . . . . . . . 3
Christopher Buckley, Lisa Alcock, Rı´ona McArdle, Rana Zia Ur Rehman, Silvia Del Din,
ClaudiaMazza`,AlisonJ.YarnallandLynnRochester
TheRoleofMovementAnalysisinDiagnosingandMonitoringNeurodegenerativeConditions:
InsightsfromGaitandPosturalControl
Reprintedfrom:BrainSci.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
Reprintedfrom:BrainSci.2019,9,30,doi:10.3390/brainsci9020030. . . . . . . . . . . . . . . . . . 36
Julio-Ce´sarGarc´ıaandRosa-HelenaBustos
TheGeneticDiagnosisofNeurodegenerativeDiseasesandTherapeuticPerspectives
Reprintedfrom:BrainSci.2018,8,222,doi:10.3390/brainsci8120222 . . . . . . . . . . . . . . . . . 51
EdwardBotsford,JayanGeorgeandEllenE.Buckley
Parkinson’sDiseaseandMetalStorageDisorders:ASystematicReview
Reprintedfrom:BrainSci.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
neurologicaldisordersinbothchildrenandadults.McNeillisidentifyingnewwaysofphenotyping
patients in order to improve diagnosis and disease monitoring, for example, through using
patient-wearable movement sensors (collaboration with INSIGNEO) in adults with neurological
disordersand3-dimensionalfacialimageanalysis(collaborationwithProfPeterHammond,Oxford)
inchildrenwithchromosomemicrodeletions. Heisalsointerestedinstudyingvariantsofuncertain
significanceasidentifiedinclinicalgeneticstesting,andresolvingtheirpathogenicitythroughclinical
phenotypingandinvitrostudies.
vii

brain
sciences
Editorial
Brain Sciences
Editorial for Special Issue: “Diagnosis
of Neurogenetic Disorders: Contribution of
Next-Generation Sequencing and Deep Phenotyping”
AlisdairMcNeill
DepartmentofNeuroscience,UniversityofSheffield,385aGlossopRoad,SheffieldS102HQ,UK;
a.mcneill@sheffield.ac.uk
Received:11March2019;Accepted:19March2019;Published:26March2019
InthisSpecialIssuewebringtogetherpapersdemonstratingtheneedforbothdetailedgenomic
andphenotypicstudiestoaidourscientificandclinicalunderstandingofneurogeneticdisorders.
Genomic techniques such as genome and exome sequencing are vital tools for diagnosing rare
neurogeneticdisordersandidentifyingnovelcausalgenes[1,2].InthisSpecialIssue,Gardnerand
colleagues[3]utilisegenomictechniquestoidentifyaseriesofindividualswithbrainmalformations
duetotherecurrentTUBA1Ap.Arg2Hisvariant.Thispaperalsodescribesthedetailedphenotyping
requiredtoaidintheinterpretationofnovelgenomicvariants.VariantsinGBA1,thegenecausing
Gaucher Disease (GD), are associated with an increased risk of Parkinson’s Disease (PD) [4,5].
Gatto andcolleaguesreviewthisimportantareaanddescribehowsimpleclinicalobservations
helpedbegintheidentificationofthisimportantriskfactorforPD[6].Genomictechniquesarecrucial
forthediagnosisofneurogeneticdisorders[7]. GarciaandBustos[8]reviewtheimpactofsuch
techniquesforboththediagnosisofneurogeneticdiseasesandincreasingourscientificunderstanding
ofthesedisorders. Itisonlythroughtheco-developmentofbothnovelgenomicandphenotypic
assessmentsthatwewillbeabletofullyunderstandthepathogenesisofneurogeneticdisordersand
identifynoveltreatments.
ConflictsofInterest:Theauthordeclaresnoconflictofinterest.
References
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neurodevelopmentaldisorderwithfeaturesofCoffin-Sirissyndrome. J.Med. Genet. 2016,53,152–162.
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Suckno,S.;Deshpande,C.;etal. MYT1Lmutationscauseintellectualdisabilityandvariableobesityby
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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.ClinicalandFunctionalCharacterizationoftheRecurrentTUBA1A
p.(Arg2His)Mutation.BrainSci.2018,8,145.[CrossRef][PubMed]
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HyposmiaandcognitiveimpairmentinGaucherdiseasepatientsandcarriers.Mov.Disord.2012,27,526–532.
[CrossRef][PubMed]
5. McNeill,A.;Duran,R.;Hughes,D.A.;Mehta,A.;Schapira,A.H.Aclinicalandfamilyhistorystudyof
Parkinson’sdiseaseinheterozygousglucocerebrosidasemutationcarriers.J.Neurol.Neurosurg.Psych.2012,
83,853–854.[CrossRef][PubMed]
BrainSci.2019,9,72;doi:10.3390/brainsci9030072 1 www.mdpi.com/journal/brainsci