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.
摘要：
我们旨在通过连锁分析和外显子组测序来确定一个有3名受影响兄弟姐妹的近亲家庭中伴有精神缺陷的神经系统疾病的遗传原因。患者大脑中铁的积累是一个显着的表型特征。全视野视网膜电图显示光感受器普遍功能障碍，双极细胞，和无长突细胞。在患者中鉴定了编码GTP结合蛋白2的GTPBP2中的剪接位点突变，并认为可能是其疾病的原因。经验表明，该突变会导致基因外显子9的缺失，并导致产生截短的缺乏蛋白质的保守C末端结构域。GTPP2是GTPase蛋白质超家族的成员。最近有报道在小鼠GTPBP2中鉴定出另一种导致神经变性的剪接位点突变，视网膜损伤为我们的发现提供了支持性证据.所研究的家庭受影响个体的状况可能会定义一种新型的具有脑铁积累的神经变性，GTPBP2可能是一种新型的脑铁蓄积神经变性基因。
