Supplementary Material for: Fahr's Disease Linked to a Novel <b><i>SLC20A2 </i></b>Gene Mutation Manifesting with Dynamic Aphasia

<b><i>Background:</i></b> Idiopathic basal ganglia calcification (IBGC), also known as Fahr's disease, is a rare disorder characterized by widespread cerebral calcifications, an autosomal dominant pattern of inheritance and clinical and genetic heterogeneity. The recently identified IBGC gene, <i>SLC20A2,</i> encodes for type III sodium-dependent phosphate transporter 2 and its loss-of-function mutations may lead to the regional accumulation of inorganic phosphate in the brain, causing calcium phosphate deposition. <b><i>Objective:</i></b> To describe the clinical, neuroimaging and genetic findings in an Italian family with IBGC. <b><i>Methods:</i></b> The family members underwent clinical and radiological examination in order to diagnose IBGC according to standard criteria and screening for <i>SLC20A2</i> gene mutations. The affected subjects also underwent neuropsychological longitudinal assessments and functional neuroimaging investigations. <b><i>Results:</i></b> The 2 affected family members harbored a novel missense mutation, G1618A, in the <i>SLC20A2</i> gene, leading to gly540-to-arg (G540R) substitution in a highly conserved residue. This is the first <i>SLC20A2 </i>gene mutation associated with familial IBGC reported in the Italian population and is damaging according to all prediction programs. In the index case we observed a fair correlation between cortical areas with no calcifications but with significant hypometabolism at [18F]FDG-PET (inferior frontal premotor cortex) and the neuropsychological picture dominated by dynamic aphasia and buccofacial apraxia. <b><i>Conclusion:</i></b> These findings expand the catalog of <i>SLC20A2</i> mutations identified to date and add dynamic aphasia to the spectrum of neuropsychological deficits reported in IBGC, supporting the use of functional neuroimaging studies for better investigation of genotype-phenotype correlations.

<b><i>背景：</i></b> 特发性基底节钙化（Idiopathic basal ganglia calcification, IBGC）又称法尔病（Fahr's disease），是一种罕见的神经系统疾病，以广泛颅内钙化为特征，呈常染色体显性遗传模式，且存在临床与遗传异质性。近期发现的IBGC致病基因<i>SLC20A2</i>编码III型钠依赖性磷酸转运蛋白2，其功能丧失性突变可导致脑内区域性无机磷酸蓄积，进而引发磷酸钙沉积。
<b><i>目的：</i></b> 本研究旨在描述一个意大利IBGC家系的临床、神经影像学及遗传学特征。
<b><i>方法：</i></b> 对该家系成员开展临床与影像学检查，依据标准诊断准则确诊IBGC，并对<i>SLC20A2</i>基因进行突变筛查；对受累患者额外实施纵向神经心理学评估与功能性神经影像学检查。
<b><i>结果：</i></b> 2名受累家系成员携带<i>SLC20A2</i>基因上一种新型错义突变G1618A，该突变导致蛋白第540位甘氨酸被精氨酸取代（G540R），突变位点位于高度保守区域。这是意大利人群中首次报道的与家族性IBGC相关的<i>SLC20A2</i>基因突变，且经所有致病性预测软件验证均判定为致病性突变。先证者的影像学结果显示，无钙化但在[18F]FDG-PET扫描中呈现显著低代谢的皮质区域（额下回运动前皮质）与以动力性失语及口面部失用为核心表现的神经心理学特征具有良好相关性。
<b><i>结论：</i></b> 本研究拓展了目前已报道的<i>SLC20A2</i>基因突变谱系，并将动力性失语纳入IBGC相关神经心理学缺陷谱，同时证实功能性神经影像学检查可用于进一步探究基因型-表型关联。

搜集汇总

背景与挑战

背景概述

该数据集是作为一篇研究论文的补充材料，聚焦于Fahr's disease（特发性基底节钙化）与SLC20A2基因新突变（G1618A，导致G540R替换）的关联，特别是在一个意大利家庭中的发现。数据集的关键特点包括：首次报道了意大利人群中与家族性IBGC相关的SLC20A2基因突变，并揭示了该突变与动态失语症等神经心理学缺陷的关联，同时通过功能神经影像（如[18F]FDG-PET）支持了基因-表型相关性的深入调查。