Identification of mutation in GTPBP2 in patients of a family with neurodegeneration accompanied by iron deposition in the brain

Neurobiol Aging. 2016 Feb;38:216.e11-216.e18. doi: 10.1016/j.neurobiolaging.2015.10.034.

Elham Jaberi ¹, Mohammad Rohani ², Gholam Ali Shahidi ², Shahriar Nafissi ³, Ehsan Arefian ¹, Masoud Soleimani ⁴, Paniz Rasooli ¹, Hamid Ahmadieh ⁵, Narsis Daftarian ⁶, Mohammad KaramiNejadRanjbar ⁷, Brandy Klotzle ⁸, Jian-Bing Fan ⁸, Casey Turk ⁸, Frank Steemers ⁸, Elahe Elahi ⁹

Affiliations

1 School of Biology, College of Sciences, University of Tehran, Tehran, Iran.
2 Department of Neurology, Hazrat Rasool Hospital, Iran University of Medical Sciences, Tehran, Iran.
3 Department of Neurology, Tehran University of Medical Sciences, Tehran, Iran.
4 School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
5 Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
6 Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
7 Department of Biotechnology, College of Sciences, University of Tehran, Tehran, Iran.
8 Illumina, San Diego, CA, USA.
9 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.

PMID: 26675814 DOI: 10.1016/j.neurobiolaging.2015.10.034

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.

Keywords

Ataxia; Cognitive dysfunction; Exome sequencing; GTPBP2; NBIA; Neurodegenerative disease.

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