Microarray analysis unmasked two siblings with pure heredita

Microarray analysis unmasked two siblings with pure hereditary spastic paraplegia shared a run of homozygosity region onchromosome 3q28–q29

JournaloftheNeurologicalSciences359(2015)351–355

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JournaloftheNeurologicalSciences

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Microarrayanalysisunmaskedtwosiblingswithpurehereditaryspasticparaplegiasharedarunofhomozygosityregiononchromosome3q28–q29

WenqianYua,1,XiangdongYoub,1,DongWanga,KaiDonga,JingSuc,ChuanfenLic,JinxiuLiua,QianqianZhanga,FengYoua,XiangrongWanga,JingHuanga,BinQiaoa, ,2,WenyuanDuana, ,2

abc

InstituteofCardiovascularDisease,GeneralHospitalofJinanMilitaryRegion,8LashanRoad,Jinan250022,China

DivisionofQualityManagement,ShandongCenterforDiseaseControlandPrevention,16992JingshiRoad,Jinan250014,ChinaDepartmentofNeurology,GeneralHospitalofJinanMilitaryRegion,25ShifanRoad,Jinan250031,China

articleinfoabstract

Hereditaryspasticparaplegia(HSP)isaclinicalandgeneticheterogeneitygroupofneurodegenerativedisorderswhichischaracterizedbyprogressiveweaknessandspasticityofthelowerlimbs.Morethan70genetictypesofHSPhavebeendescribedsofar.HerewedescribeaChinesenon-consanguineousfamilywithtwoaffectedsiblingsmanifestingearly-onsetautosomalrecessiveHSPinpureforms.Toidentifygenotypeandcharacterizephenotype,CytoScanHDarrayanalysiswasperformedonthetwosiblings.Arunofhomozygosity(ROH)sharedbythetwopatientswasdetectedonchromosome3q28–q29.TheROHregion,about7.7Mbonthechromosome3:190172058-197851260partiallyoverlappedwiththeROHregionofSPG14previouslyreported.Subsequently,microsatelliteanalysiscon rmedthisROHandwhole-exomesequencingwascarriedoutwhilenocausativemu-tationswerefoundintheexonsofknownHSPgenesand68candidategenesinthatregion.Inconclusion,ourdatasuggesttheROHinthisregionmayplayapivotalroleinSPG14pathogenesis.Thisisthe rstclinicaldescriptionofapureformspasticparaplegiainanon-consanguineousfamilyassociatedwiththeSPG14locus.

©2015ElsevierB.V.Allrightsreserved.

Articlehistory:

Received12January2015

Receivedinrevisedform21October2015Accepted27October2015

Availableonline4November2015Keywords:

HereditaryspasticparaplegiaMicroarray3q28–q29

RunofhomozygositySPG14

Autosomalrecessive

Neurodegenerativedisorder

1.Introduction

Hereditaryspasticparaplegia(HSP)isoneofthemostclinicallyandgeneticallyheterogeneousgroupsofinheritedneurodegenerativedisordersmainlycharacterizedbyslowlyprogressivelower-limbspas-ticitywhichworsensovertime.Theneuropathologic ndingistheresultofthelongmotoraxonsofthecorticospinal-tractdegeneration[1–3].Themodesofinheritanceincludeautosomaldominant(AD-HSP),autosomalrecessive(AR-HSP),X-linkedormitochondrialtrait[4,5].Clinically,HSPsareclassi edaspureandcomplicatedforms.ThecomplicatedHSPsarecombinedwithfurtherneurologicalandsystemicabnormalities,whereasthepureformsessentiallyexhibitedlowerlimbweaknessandspasticity.Todate,morethan70differentlocihavebeenmappedand55spasticparaplegiagenes(SPGs)wereidenti ed.ThecorrespondingproteinsofSPGsplaykeyrolesintheregulationofintracellularmembranetraf cking,endoplasmicreticulummembrane

shaping,DNArepair,autophagy,mitochondrialfunction,lipidmetabo-lismandmyelinformation[6–8].

SPG14isanautosomalrecessiveformofHSPwhichhasbeenmappedtoacandidatediseaselocusonchromosome3q27–q28be-tweenmarkersD3S1580(chr3:188542793–188543136)andD3S3669(chr3:192501965–192502314)[9].Bynowonlyasingleconsanguine-ousItalianfamilywiththreeaffectedsubjectspresentingacomplexphenotypeincludingmildmentalretardationandmilddistalmotorneuropathyhasbeendescribed.

Herein,wereportedtwosiblingsborninanon-consanguineousChinesefamilywithspasticparaplegia.TheclinicalmanifestationsofourpatientspresentapureformofHSP.SNPmicroarraycon rmedanROHonchromosome3q28–q29ofthetwoaffectedsiblingsthatpartiallycoincidedwiththeregionofSPG14inthepreviousreport.2.Patientsandmethods2.1.Patients

Correspondingauthors.

E-mailaddresses:cijnmd@(B.Qiao),dwy2115@(W.Duan).1

The rsttwoauthorscontributedequallytothiswork.2

Thetwocorrespondingauthorscontributedequallytothis

work.

Thepresentstudyinvolvedtwosiblingsfromafamilywithpurespasticparaplegia.ThefamilypedigreeisshowninFig.1.Theirparentsarenon-consanguineousmarriage,andtheirfatherdiedofcirrhosis

/10.1016/j.jns.2015.10.057

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