title: Identification of mutation in GTPBP2 in patients of a family with neurodegeneration accompanied by iron deposition in the brain.
abstract: We aimed to identify the genetic cause of a neurologic disorder accompanied with mental deficiency in a consanguineous family with 3 affected siblings by linkage analysis and exome sequencing. Iron accumulation in the brain of the patients was a notable phenotypic feature. A full-field electroretinography revealed generalized dysfunction of photoreceptors, bipolar cells, and amacrine cells. A splice site mutation in GTPBP2 that encodes GTP-binding protein 2 was identified in the patients and considered possible cause of their disease. The mutation was empirically shown to cause deletion of exon 9 of the gene and result in production of a truncated protein-lacking conserved C-terminus domains. GTPBP2 is a member of the GTPase superfamily of proteins. A recent report of identification of another splice site mutation in GTPBP2 in mice that causes neurodegeneration, and retinal damage provides supportive evidence for our finding. The conditions in the affected individuals of the family studied may define a novel form of neurodegeneration with brain iron accumulation, and GTPBP2 may be a novel neurodegeneration with brain iron accumulation gene.
authors.affiliation: School of Biology, College of Sciences, University of Tehran, Tehran, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Jaberi
authors.affiliation: Department of Neurology, Hazrat Rasool Hospital, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rohani
authors.affiliation: Department of Neurology, Hazrat Rasool Hospital, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Gholam Ali
authors.initials: GA
authors.lastname: Shahidi
authors.affiliation: Department of Neurology, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shahriar
authors.initials: S
authors.lastname: Nafissi
authors.affiliation: School of Biology, College of Sciences, University of Tehran, Tehran, Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Arefian
authors.affiliation: School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: School of Biology, College of Sciences, University of Tehran, Tehran, Iran.
authors.forename: Paniz
authors.initials: P
authors.lastname: Rasooli
authors.affiliation: Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Ahmadieh
authors.affiliation: Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Narsis
authors.initials: N
authors.lastname: Daftarian
authors.affiliation: Department of Biotechnology, College of Sciences, University of Tehran, Tehran, Iran.
authors.forename: Eli M
authors.initials: EM
authors.lastname: Carrami
authors.affiliation: Illumina, San Diego, CA, USA.
authors.forename: Brandy
authors.initials: B
authors.lastname: Klotzle
authors.affiliation: Illumina, San Diego, CA, USA.
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.affiliation: Illumina, San Diego, CA, USA.
authors.forename: Casey
authors.initials: C
authors.lastname: Turk
authors.affiliation: Illumina, San Diego, CA, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Steemers
authors.affiliation: School of Biology, College of Sciences, University of Tehran, Tehran, Iran; Department of Biotechnology, College of Sciences, University of Tehran, Tehran, Iran. Electronic address: elahe.elahi@gmail.com.
authors.forename: Elahe
authors.initials: E
authors.lastname: Elahi
mesh_terms: D000328:Adult; D000818:Animals; D001921:Brain / Q000378:metabolism*; D059472:Exome / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D019204:GTP-Binding Proteins; D056726:Genetic Association Studies; D008040:Genetic Linkage; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D051379:Mice; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics*; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism*; D017422:Sequence Analysis, DNA
chemical_list: D007501:Iron; D019204:GTP-Binding Proteins; C410338:GTPBP2 protein, human; D020559:Monomeric GTP-Binding Proteins
keywords: Ataxia; Cognitive dysfunction; Exome sequencing; GTPBP2; NBIA; Neurodegenerative disease