Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification.
Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification.
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DOI：
10.1007/s10048-012-0349-2
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发表时间：
2013-02
期刊：
影响因子：
2.2
通讯作者：
Coppola, Giovanni
中科院分区：
文献类型：
--
作者：
Hsu, Sandy Chan;Sears, Renee L.;Lemos, Roberta R.;Quintans, Beatriz;Huang, Alden;Spiteri, Elizabeth;Nevarez, Lisette;Mamah, Catherine;Zatz, Mayana;Pierce, Kerrie D.;Fullerton, Janice M.;Adair, John C.;Berner, Jon E.;Bower, Matthew;Brodaty, Henry;Carmona, Olga;Dobricic, Valerija;Fogel, Brent L.;Garcia-Estevez, Daniel;Goldman, Jill;Goudreau, John L.;Hopfer, Suellen;Jankovic, Milena;Jauma, Serge;Jen, Joanna C.;Kirdlarp, Suppachok;Klepper, Joerg;Kostic, Vladimir;Lang, Anthony E.;Linglart, Agnes;Maisenbacher, Melissa K.;Manyam, Bala V.;Mazzoni, Pietro;Miedzybrodzka, Zofia;Mitarnun, Witoon;Mitchell, Philip B.;Mueller, Jennifer;Novakovic, Ivana;Paucar, Martin;Paulson, Henry;Simpson, Sheila A.;Svenningsson, Per;Tuite, Paul;Vitek, Jerrold;Wetchaphanphesat, Suppachok;Williams, Charles;Yang, Michele;Schofield, Peter R.;de Oliveira, Joao R. M.;Sobrido, Maria-Jesus;Geschwind, Daniel H.;Coppola, Giovanni
家族性特发性基底神经节钙化（IBGC）或法赫尔病是一种罕见的神经退行性疾病，其特征是基底神经节和其他大脑区域钙沉积，与神经精神和运动症状相关。家族性 IBGC 具有遗传异质性，通常以常染色体显性遗传方式传播。我们对第一个被发现导致 IBGC 的基因 SLC20A2 进行了突变分析，以评估其对家族性 IBGC 的遗传贡献。我们从 29 个不同血统的 IBGC 受影响家庭中招募了 218 名受试者，并收集了病史、神经系统检查和头部 CT 扫描，以表征每位患者的疾病状况。我们对患者队列进行了 SLC20A2 突变筛查。在 13 个家族中鉴定出 12 个新的（无义、缺失、错义和剪接位点）潜在致病变异、1 个同义变异和 1 个先前报道的突变。预计变异体是有害的，与五个家族的疾病共分离。三个家族表现出此类变异的临床疾病不分离，但临床和神经影像数据的回顾性审查强烈表明以前的错误分类。总体而言，SLC20A2 突变占我们家族性 IBGC 病例的 41%。我们的大规模系列筛查扩展了迄今为止已发现的 SLC20A2 突变目录，并证明 SLC20A2 突变是家族性 IBGC 的主要原因。预测的有害变异的不完美分离模式凸显了这种临床表现高度可变的情况下表型评估的挑战。
Familial idiopathic basal ganglia calcification (IBGC) or Fahr’s disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient’s disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation.
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影响因子：
6
作者：
Kostic, Vladimir S.;Lukic-Jecmenica, Milica;Pavlovic, Aleksandra
通讯作者：
Pavlovic, Aleksandra
影响因子：
14.9
作者：
Desmet FO;Hamroun D;Lalande M;Collod-Béroud G;Claustres M;Béroud C
通讯作者：
Béroud C
影响因子：
5.3
作者：
Brodaty, H;Mitchell, P;Schofield, PR
通讯作者：
Schofield, PR
影响因子：
3.1
作者：
Volpato, Claudia Beu;De Grandi, Alessandro;Pramstaller, Peter P.
通讯作者：
Pramstaller, Peter P.
影响因子：
30.8
作者：
Wang, Cheng;Li, Yulei;Liu, Jing-Yu
通讯作者：
Liu, Jing-Yu