背景:脑钙化是影像学上常见的发现。在一小部分案件中,这些钙化与致病基因变异有关,因此称为原发性家族性脑钙化(PFBC)。临床外显率不完全,表型变异性很大。本文旨在描述瑞典PFBC队列的特征,其中包括25例患者:来自7个家庭的20例和5例零星病例。
方法:进行纵向临床评估和CT成像,异常使用总钙化评分(TCS)进行评估.遗传分析,包括一组六个已知的PFBC基因,在所有索引和零星病例中进行。此外,对3例携带SLC20A2新型致病基因拷贝数变异体的患者的脑脊液磷酸盐(CSF-Pi)水平进行了检测.
结果:在25名患者中,大多数(76%)在初始评估中表现出不同的症状,包括运动(60%),精神病(40%),和/或认知异常(24%)。在大多数患者中观察到临床进展(78.6%),但是第一次和第二次扫描之间的钙化没有显着差异,平均得分为27.3分和32.8分。在三个家庭和两个零星案件中,确定了致病性遗传变异,包括一个新颖的发现,在SLC20A2基因中。在三个被测试的病人中,CSF-Pi水平正常。
结论:该报告证明了在PFBC中观察到的可变表达,并包括SLC20A2基因中的新致病变异。在四个家庭和三个零星病例中,没有发现致病变异,这表明新的PFBC基因仍有待发现。
BACKGROUND: Brain calcifications are frequent findings on imaging. In a small proportion of cases, these calcifications are associated with pathogenic gene variants, hence termed primary familial brain calcification (PFBC). The clinical penetrance is incomplete and phenotypic variability is substantial. This paper aims to characterize a Swedish PFBC cohort including 25 patients: 20 from seven families and five sporadic cases.
METHODS: Longitudinal clinical assessment and CT imaging were conducted, abnormalities were assessed using the total calcification score (TCS). Genetic analyses, including a panel of six known PFBC genes, were performed in all index and sporadic cases. Additionally, three patients carrying a novel pathogenic copy number variant in SLC20A2 had their cerebrospinal fluid phosphate (CSF-Pi) levels measured.
RESULTS: Among the 25 patients, the majority (76%) displayed varying symptoms during the initial assessment including motor (60%), psychiatric (40%), and/or cognitive abnormalities (24%). Clinical progression was observed in most patients (78.6%), but there was no significant difference in calcification between the first and second scans, with mean scores of 27.3 and 32.8, respectively. In three families and two sporadic cases, pathogenic genetic variants were identified, including a novel finding, in the SLC20A2 gene. In the three tested patients, the CSF-Pi levels were normal.
CONCLUSIONS: This report demonstrates the variable expressivity seen in PFBC and includes a novel pathogenic variant in the SLC20A2 gene. In four families and three sporadic cases, no pathogenic variants were found, suggesting that new PFBC genes remain to be discovered.