Grütz Karen, Volpato Claudia B, Domingo Aloysius, Alvarez-Fischer Daniel, Gebert Uwe, Schifferle Günther, Buffone Ebba, Wszolek Zbigniew K, Rademakers Rosa, Ferbert Andreas, Hicks Andrew A, Klein Christine, Pramstaller Peter P, Westenberger Ana
Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy-Affiliated Institute of the University of Lübeck, Lübeck, Germany.
Mov Disord. 2016 Dec;31(12):1901-1904. doi: 10.1002/mds.26768. Epub 2016 Sep 27.
Linkage analyses of families with primary familial brain calcification (formerly idiopathic basal ganglia calcification [IBGC]) identified 3 candidate loci (IBGC1-3). Recently, SLC20A2 mutations were found in the IBGC1 and IBGC3 families, merging these 2 loci. We here elucidate the genetic cause of primary familial brain calcification in the 'IBGC2' kindred.
We sequenced known primary familial brain calcification genes and quantified SLC20A2 and PDGFB. Moreover, CT scans of affected and unaffected family members were evaluated by 2 blinded neuroradiologists for distribution of brain calcification.
A heterozygous multiexonic SLC20A2 deletion was detected in several affected family members. A reevaluation of neuroimaging data revealed a subset of mutation-negative individuals with only mild and/or unilateral calcification.
The identified SLC20A2 mutation resolves the genetic cause of primary familial brain calcification in the 'IBGC2' kindred, collapsing 'IBGC2' into IBGC1. We suggest an algorithm for predicting the chances of finding genetic mutations that has to be validated in further studies. Our study enhances criteria for the evaluation of neuroimaging data, contributing further to the much needed harmonization of diagnostic and research data collection in primary familial brain calcification. © 2016 International Parkinson and Movement Disorder Society.
对原发性家族性脑钙化（原特发性基底节钙化[IBGC]）家系进行连锁分析，确定了3个候选基因座（IBGC1 - 3）。最近，在IBGC1和IBGC3家系中发现了SLC20A2突变，合并了这2个基因座。我们在此阐明“IBGC2”家系中原发性家族性脑钙化的遗传原因。
我们对已知的原发性家族性脑钙化基因进行测序，并对SLC20A2和PDGFB进行定量分析。此外，2名不知情的神经放射科医生对患病和未患病家庭成员的CT扫描结果进行评估，以确定脑钙化的分布情况。
在几名患病家庭成员中检测到杂合的多外显子SLC20A2缺失。对神经影像学数据的重新评估显示，有一部分突变阴性个体仅存在轻度和/或单侧钙化。
所鉴定的SLC20A2突变解决了“IBGC2”家系中原发性家族性脑钙化的遗传原因，将“IBGC2”并入IBGC1。我们提出了一种预测发现基因突变可能性的算法，该算法有待在进一步研究中验证。我们的研究完善了神经影像学数据的评估标准，进一步有助于实现原发性家族性脑钙化诊断和研究数据收集急需的标准化。© 2016国际帕金森病和运动障碍协会。
