Please use this identifier to cite or link to this item: https://doi.org/10.1242/dmm.026476
DC FieldValue
dc.titleA homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy
dc.contributor.authorSeco, C.Z
dc.contributor.authorCastells-Noba A.
dc.contributor.authorJoo, S.-H
dc.contributor.authorSchraders, M.
dc.contributor.authorFoo, J.N.
dc.contributor.authorVan Der Voet, M.
dc.contributor.authorVelan, S.S
dc.contributor.authorNijhof, B.
dc.contributor.authorOostrik, J.
dc.contributor.authorDe Vrieze, E.
dc.contributor.authorKatana, R.
dc.contributor.authorMansoor, A.
dc.contributor.authorHuynen, M.
dc.contributor.authorSzklarczyk, R.
dc.contributor.authorOti, M.
dc.contributor.authorTranebjarg, L.
dc.contributor.authorVan Wijk, E.
dc.contributor.authorScheffer-De Gooyert, J.M.
dc.contributor.authorSiddique, S.
dc.contributor.authorBaets, J.
dc.contributor.authorDe Jonghe, P.
dc.contributor.authorKazmi, S.A.R.
dc.contributor.authorSadananthan, S.A
dc.contributor.authorVan De Warrenburg, B.P.
dc.contributor.authorKhor, C.C
dc.contributor.authorGöpfert, M.C.
dc.contributor.authorQamar, R.
dc.contributor.authorSchenck, A.
dc.contributor.authorKremer, H.
dc.contributor.authorSiddiqi, S.
dc.date.accessioned2020-09-01T00:56:30Z
dc.date.available2020-09-01T00:56:30Z
dc.date.issued2017
dc.identifier.citationSeco, C.Z, Castells-Noba A., Joo, S.-H, Schraders, M., Foo, J.N., Van Der Voet, M., Velan, S.S, Nijhof, B., Oostrik, J., De Vrieze, E., Katana, R., Mansoor, A., Huynen, M., Szklarczyk, R., Oti, M., Tranebjarg, L., Van Wijk, E., Scheffer-De Gooyert, J.M., Siddique, S., Baets, J., De Jonghe, P., Kazmi, S.A.R., Sadananthan, S.A, Van De Warrenburg, B.P., Khor, C.C, Göpfert, M.C., Qamar, R., Schenck, A., Kremer, H., Siddiqi, S. (2017). A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy. DMM Disease Models and Mechanisms 10 (2) : 105-118. ScholarBank@NUS Repository. https://doi.org/10.1242/dmm.026476
dc.identifier.issn17548403
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/173796
dc.description.abstractA consanguineous family from Pakistan was ascertained to have a novel deafness-dystonia syndrome with motor regression, ichthyosislike features and signs of sensory neuropathy. By applying a combined strategy of linkage analysis and whole-exome sequencing in the presented family, a homozygous nonsense mutation, c.4G>T (p.Glu2?), in FITM2 was identified. FITM2 and its paralog FITM1 constitute an evolutionary conserved protein family involved in partitioning of triglycerides into cellular lipid droplets. Despite the role of FITM2 in neutral lipid storage and metabolism, no indications for lipodystrophy were observed in the affected individuals. In order to obtain independent evidence for the involvement of FITM2 in the human pathology, downregulation of the single Fitm ortholog, CG10671, in Drosophila melanogaster was pursued using RNA interference. Characteristics of the syndrome, including progressive locomotor impairment, hearing loss and disturbed sensory functions, were recapitulated in Drosophila, which supports the causative nature of the FITM2 mutation.Mutation-based genetic counseling can now be provided to the family and insight is obtained into the potential impact of genetic variation in FITM2. © 2017. Published by The Company of Biologists Ltd.
dc.sourceUnpaywall 20200831
dc.subjectaspartate aminotransferase
dc.subjectcreatine kinase
dc.subjectfitm2 protein
dc.subjectlactate dehydrogenase
dc.subjectprotein
dc.subjectunclassified drug
dc.subjectDrosophila protein
dc.subjectfat droplet
dc.subjectFIT2 protein, human
dc.subjectmembrane protein
dc.subjectadolescent
dc.subjectadult
dc.subjectArticle
dc.subjectchild
dc.subjectclinical article
dc.subjectclinical examination
dc.subjectclinical observation
dc.subjectDrosophila melanogaster
dc.subjectdystonia
dc.subjectfat content
dc.subjectfemale
dc.subjectfruit fly model
dc.subjectgene mutation
dc.subjectgenetic counseling
dc.subjectgenetic variation
dc.subjecthearing impairment
dc.subjecthomozygosity
dc.subjecthuman
dc.subjectichthyosis
dc.subjectlipid storage
dc.subjectloss of function mutation
dc.subjectmale
dc.subjectnonsense mutation
dc.subjectPakistani
dc.subjectperception deafness
dc.subjectphenotype
dc.subjectpriority journal
dc.subjectprotein expression
dc.subjectpure tone audiometry
dc.subjectsensory neuropathy
dc.subjecttympanometry
dc.subjectwhole exome sequencing
dc.subjectanimal
dc.subjectblood
dc.subjectcomplication
dc.subjectdeafblindness
dc.subjectdisease model
dc.subjectdystonia
dc.subjectgene expression regulation
dc.subjectgene silencing
dc.subjectgenetics
dc.subjecthearing impairment
dc.subjectHEK293 cell line
dc.subjecthomozygote
dc.subjectichthyosis
dc.subjectintellectual impairment
dc.subjectliver
dc.subjectlocomotion
dc.subjectmetabolism
dc.subjectmotor activity
dc.subjectmutation
dc.subjectnucleotide sequence
dc.subjectobesity
dc.subjectoptic nerve atrophy
dc.subjectpathology
dc.subjectpathophysiology
dc.subjectpedigree
dc.subjectsensory nerve cell
dc.subjectstop codon
dc.subjectyoung adult
dc.subjectAdiposity
dc.subjectAnimals
dc.subjectAudiometry, Pure-Tone
dc.subjectBase Sequence
dc.subjectChild
dc.subjectCodon, Nonsense
dc.subjectDeaf-Blind Disorders
dc.subjectDisease Models, Animal
dc.subjectDrosophila melanogaster
dc.subjectDrosophila Proteins
dc.subjectDystonia
dc.subjectFemale
dc.subjectGene Expression Regulation
dc.subjectGene Knockdown Techniques
dc.subjectHearing Loss
dc.subjectHEK293 Cells
dc.subjectHomozygote
dc.subjectHumans
dc.subjectIchthyosis
dc.subjectIntellectual Disability
dc.subjectLipid Droplets
dc.subjectLiver
dc.subjectLocomotion
dc.subjectMale
dc.subjectMembrane Proteins
dc.subjectMotor Activity
dc.subjectMutation
dc.subjectOptic Atrophy
dc.subjectPedigree
dc.subjectSensory Receptor Cells
dc.subjectWhole Exome Sequencing
dc.subjectYoung Adult
dc.typeArticle
dc.contributor.departmentDEPT OF MEDICINE
dc.contributor.departmentDEPT OF OBSTETRICS & GYNAECOLOGY
dc.contributor.departmentDEPT OF BIOCHEMISTRY
dc.description.doi10.1242/dmm.026476
dc.description.sourcetitleDMM Disease Models and Mechanisms
dc.description.volume10
dc.description.issue2
dc.description.page105-118
Appears in Collections:Staff Publications
Elements

Show simple item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1242_dmm_026476.pdf3.61 MBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.