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One novel GRN null mutation, two different aphasia phenotypes
Neurobiology of Aging ( IF 4.2 ) Pub Date : 2020-03-01 , DOI: 10.1016/j.neurobiolaging.2019.11.008
Cinzia Coppola 1 , Mariano Oliva 1 , Dario Saracino 1 , Sabina Pappatà 2 , Emilia Zampella 3 , Sara Cimini 4 , Martina Ricci 4 , Giorgio Giaccone 4 , Giuseppe Di Iorio 1 , Giacomina Rossi 4
Affiliation  

Progranulin gene (GRN) mutations are among the leading causes of frontotemporal lobar degeneration, a group of neurodegenerative diseases characterized by remarkable clinical heterogeneity. In this article, we report the new GRN 708+4A>T splicing mutation, identified in 2 siblings of a family with several members affected by cognitive, behavioral, and motor disorders. Plasma progranulin dosage and GRN expression analysis, together with in silico prediction studies, supported the pathogenicity of the mutation. Both the patients displayed a clinical syndrome in which language impairment was largely predominant. However, motor speech deficits were the major feature in one case, diagnosed as progressive nonfluent aphasia, whereas marked semantic alterations were present in the other, whose clinical phenotype was in favor of a mixed aphasia. The profile of neuroanatomical alterations from imaging studies was in line with the clinical phenotypes. Therefore, also this novel GRN mutation is associated with haploinsufficiency and phenotypic heterogeneity, which are both typical features of progranulinopathies.

中文翻译:

一种新的 GRN 无效突变,两种不同的失语症表型

颗粒蛋白前体基因 (GRN) 突变是额颞叶变性的主要原因之一,额颞叶变性是一组具有显着临床异质性特征的神经退行性疾病。在本文中,我们报告了新的 GRN 708+4A>T 剪接突变,该突变在一个家族的 2 个兄弟姐妹中发现,该家族的几个成员受到认知、行为和运动障碍的影响。血浆颗粒蛋白前体剂量和 GRN 表达分析以及计算机预测研究支持突变的致病性。这两名患者都表现出一种临床综合征,其中语言障碍在很大程度上是主要的。然而,在一个病例中,运动语言缺陷是主要特征,被诊断为进行性非流利性失语症,而在另一个病例中存在明显的语义改变,其临床表型有利于混合性失语症。影像学研究的神经解剖学改变与临床表型一致。因此,这种新的 GRN 突变也与单倍体不足和表型异质性相关,这两个都是颗粒蛋白原病的典型特征。
更新日期:2020-03-01
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