Publication:
VPS13D-based disease: expansion of the clinical phenotype in two brothers and mutation diversity in the Turkish population

dc.contributor.coauthorOztop-Cakmak, O.
dc.contributor.coauthorSimsir, G.
dc.contributor.coauthorTekgul, S.
dc.contributor.coauthorAygun, M. S.
dc.contributor.coauthorGokler, O.
dc.contributor.coauthorKahyaoglu, B.
dc.contributor.coauthorKaya, Z. E.
dc.contributor.coauthorPalvadeau, R.
dc.contributor.coauthorBasak, A. N.
dc.contributor.coauthorErtan, S.
dc.contributor.departmentKUTTAM (Koç University Research Center for Translational Medicine)
dc.contributor.departmentGraduate School of Sciences and Engineering
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorPalvadeau, Robin Jerome
dc.contributor.kuauthorÇakmak, Özgür Öztop
dc.contributor.kuauthorBaşak, Ayşe Nazlı
dc.contributor.kuauthorErtan, Fatoş Sibel
dc.contributor.kuauthorGökler, Ozan
dc.contributor.kuauthorŞimşir, Gülşah
dc.contributor.kuauthorAygün, Murat Serhat
dc.contributor.kuauthorTekgül, Şeyma
dc.contributor.schoolcollegeinstituteGRADUATE SCHOOL OF SCIENCES AND ENGINEERING
dc.contributor.schoolcollegeinstituteResearch Center
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2025-01-19T10:33:35Z
dc.date.issued2022
dc.description.abstractVPS13D is a recently described gene. Worldwide, only 15 families with 23 affected individuals have been reported with a VPS13D-based disease. Mutated VPS13D causes a complex phenotype with a hyperkinetic movement disorder and ataxia, especially in childhood onset disease. The clinical phenotype of the rare adult-onset cases consists of cerebellar ataxia and/or spastic paraplegia. Here, we report the extensive clinical, laboratory and genetic findings of two offspring from consanguineous parents, with ages of disease onset at 57 and 49 with VPS13D-based ataxia. Although conventional magnetic resonance imaging showed mild cerebellar and cerebral atrophy, diffusion tensor imaging, applied for the first time for VPS13D patients, revealed prominent atrophy in U fibers and cerebellopontine tracts. Whole exome sequencing analysis revealed a biallelic Ala4210Val mutation in the VPS13D, reported only once in the literature. Complementary screening of our in-house database consisting of 295 ataxia and hereditary spastic paraplegia patients revealed two further ataxia patients with novel VPS13D variants. Screening the control cohort for VPS13D variants revealed one asymptomatic individual carrying a novel VPS13D variant. In this study, the phenotypic spectrum of VPS13D-based disease is expanded with the description of pre-senile onset predominant ataxia. Further, with the additional novel mutations described, the report is expected to contribute to the understanding of the yet elusive phenotype-genotype correlations in the rare VPS13D-based movement disorder. (C) 2022 Elsevier Masson SAS. All rights reserved.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue9
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipThis work was supported by Koc University KUTTAM [Suna and Inan Kirac Foundation Istanbul Turkey, grant number 2018-2021].
dc.description.volume178
dc.identifier.doi10.1016/j.neurol.2022.05.005
dc.identifier.eissn2213-0004
dc.identifier.issn0035-3787
dc.identifier.quartileQ2
dc.identifier.scopus2-s2.0-85139328783
dc.identifier.urihttps://doi.org/10.1016/j.neurol.2022.05.005
dc.identifier.urihttps://hdl.handle.net/20.500.14288/26634
dc.identifier.wos1043676900006
dc.keywordsSCAR4
dc.keywordsLate adult-onset recessive ataxia
dc.keywordsVPS13D
dc.keywordsDTI
dc.keywordsWES
dc.language.isoeng
dc.publisherMasson Editeur
dc.relation.grantnoKoc University KUTTAM [Suna and Inan Kirac Foundation Istanbul Turkey] [2018-2021]
dc.relation.ispartofRevue Neurologique
dc.subjectClinical neurology
dc.titleVPS13D-based disease: expansion of the clinical phenotype in two brothers and mutation diversity in the Turkish population
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorÇakmak, Özgür Öztop
local.contributor.kuauthorŞimşir, Gülşah
local.contributor.kuauthorTekgül, Şeyma
local.contributor.kuauthorAygün, Murat Serhat
local.contributor.kuauthorGökler, Ozan
local.contributor.kuauthorPalvadeau, Robin Jerome
local.contributor.kuauthorBaşak, Ayşe Nazlı
local.contributor.kuauthorErtan, Fatoş Sibel
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit1GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
local.publication.orgunit1Research Center
local.publication.orgunit2KUTTAM (Koç University Research Center for Translational Medicine)
local.publication.orgunit2School of Medicine
local.publication.orgunit2Graduate School of Sciences and Engineering
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