Journal of Biotechnology & Biomaterials
Open Access

Abstract

Introduction: Whole-exome sequencing (WES) is application of the next-generation technology to determine the variations of all coding regions, or exons, of known genes. The role of more than 150 genes has been distinguished by means of WES, and this statistics is quickly growing. Purpose: We aimed to identify the genetic cause of a neurodegenerative disorder accompanied with mental deficiency in three affected siblings by linkage analysis and exome sequencing. Methods & Materials: Clinical data on the patients was gathered by interviews with parents, neurological examinations, imaging, and laboratory tests. Genetic analysis was performed by genome-wide SNP linkage analysis and exome sequencing. Effect of putative disease causing mutation was assessed by RT-PCR on RNA extracted from leukocytes, Western blotting on proteins extracted from HEK293 cells transfected with wild type and mutated genes, and immunocytochemistry on the same cells. Results: Iron accumulation in the brain of the patients was a notable phenotypic feature. A splice site mutation in GTPBP2 that encodes GTP binding protein 2 was identified as the cause of disease. Discussion: GTPBP2 is a member of a family within the GTPase superfamily of proteins which has maximum homology with members of another family that includes translation factor proteins. A recent report of a similar splice site mutation in GTPBP2 in mice that causes neurodegeneration and disruptions in protein translation provides supportive evidence for our finding. The conditions in the affected individuals studied may define a novel form of neurodegeneration with brain iron accumulation (NBIA), and GTPBP2 may be a novel NBIA gene.

Biography

Email: elham_j1981@yahoo.com