Please use this identifier to cite or link to this item: https://doi.org/10.1242/dmm.026476
Title: A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy
Authors: Seco, 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.
Keywords: aspartate aminotransferase
creatine kinase
fitm2 protein
lactate dehydrogenase
protein
unclassified drug
Drosophila protein
fat droplet
FIT2 protein, human
membrane protein
adolescent
adult
Article
child
clinical article
clinical examination
clinical observation
Drosophila melanogaster
dystonia
fat content
female
fruit fly model
gene mutation
genetic counseling
genetic variation
hearing impairment
homozygosity
human
ichthyosis
lipid storage
loss of function mutation
male
nonsense mutation
Pakistani
perception deafness
phenotype
priority journal
protein expression
pure tone audiometry
sensory neuropathy
tympanometry
whole exome sequencing
animal
blood
complication
deafblindness
disease model
dystonia
gene expression regulation
gene silencing
genetics
hearing impairment
HEK293 cell line
homozygote
ichthyosis
intellectual impairment
liver
locomotion
metabolism
motor activity
mutation
nucleotide sequence
obesity
optic nerve atrophy
pathology
pathophysiology
pedigree
sensory nerve cell
stop codon
young adult
Adiposity
Animals
Audiometry, Pure-Tone
Base Sequence
Child
Codon, Nonsense
Deaf-Blind Disorders
Disease Models, Animal
Drosophila melanogaster
Drosophila Proteins
Dystonia
Female
Gene Expression Regulation
Gene Knockdown Techniques
Hearing Loss
HEK293 Cells
Homozygote
Humans
Ichthyosis
Intellectual Disability
Lipid Droplets
Liver
Locomotion
Male
Membrane Proteins
Motor Activity
Mutation
Optic Atrophy
Pedigree
Sensory Receptor Cells
Whole Exome Sequencing
Young Adult
Issue Date: 2017
Citation: Seco, 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
Abstract: A 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.
Source Title: DMM Disease Models and Mechanisms
URI: https://scholarbank.nus.edu.sg/handle/10635/173796
ISSN: 17548403
DOI: 10.1242/dmm.026476
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