Identification of Mutation in Gtpbp2 in Patients of a Family With Neurodegeneration Accompanied by Iron Deposition in the Brain Publisher Pubmed



Jaberi E¹ ; Rohani M² ; Shahidi GA² ; Nafissi S³ ; Arefian E¹ ; Soleimani M⁴ ; Rasooli P¹ ; Ahmadieh H⁵ ; Daftarian N⁶ ; Carrami EM⁷ ; Klotzle B⁸ ; Fan JB⁸ ; Turk C⁸ ; Steemers F⁸ Show All Authors Show Affiliations
Source: Neurobiology of Aging Published:2016

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. © 2016 Elsevier Inc.