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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 |
| Appears in Collections: | Staff Publications Elements |
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