Valosin-containing protein Asp395Gly mutation in a patient with frontotemporal dementia: a case report.
Valosin-containing protein Asp395Gly mutation in a patient with frontotemporal dementia: a case report.
复制标题
DOI：
10.1186/s12883-022-02951-4
复制
发表时间：
2022-11-03
期刊：
影响因子：
2.6
通讯作者：
Otani, Koichi
中科院分区：
文献类型：
--
作者：
Kobayashi, Ryota;Naruse, Hiroya;Kawakatsu, Shinobu;Iseki, Chifumi;Suzuki, Yuya;Koyama, Shingo;Morioka, Daichi;Ishiura, Hiroyuki;Mitsui, Jun;Ohta, Yasuyuki;Tsuji, Shoji;Toda, Tatsushi;Otani, Koichi
关键词：
含缬氨肽蛋白（VCP）基因的变异被确定为与骨佩吉特病和额颞叶痴呆（FTD）相关的包涵体肌病的原因之一。先前鉴定的VCP致病性变体在病理学上与额颞叶变性伴TDP-43包涵体（FTLD-TDP）相关，但最近报告p.Asp395Gly VCP引起家族性FTD伴tau病变，其特征为神经元tau缠结（NFT），而非FTLD-TDP。我们描述了1例p.Asp395Gly缬氨肽蛋白（VCP）患者的临床和遗传学结果，该患者被诊断为FTD，无家族史且无肌肉或骨骼疾病合并症。患者为62岁男性，37岁时出现非典型抑郁症。随后，他在45岁时表现出以自我为中心的行为。自我中心的行为从50岁左右开始加剧，伴随着执行功能障碍的发展;因此，他在52岁时来到我院。磁共振成像显示双侧额叶萎缩。脑灌注单光子发射计算机断层扫描显示双侧额叶灌注不足。患者符合FTD行为变异体的诊断标准。诊断十年后，躯干和四肢的计算机断层扫描，肌肉活检和骨造影显示没有伴随的肌肉和骨骼疾病。脑脊液（CSF）总tau和磷酸化tau蛋白的浓度分别为389 pg/mL和53.2 pg/mL（临界值：50 pg/mL）。使用全外显子组和桑格测序方法进行遗传分析。我们在该患者中用纯FTD鉴定了p.Asp395Gly VCP。在1例可能为散发性FTD且无伴随肌肉和骨骼疾病的患者中发现p.Asp395Gly VCP。CSF分析表明，我们的患者可能因NFT蓄积而发生FTD，与最近报告的p.Asp395Gly VCP家族性FTD患者相似。我们的研究结果表明，不仅应考虑对家族性FTD进行VCP致病性变体的基因搜索，而且还应考虑对散发性FTD患者进行基因搜索，即使在没有共病肌肉或骨骼疾病的情况下也是如此。在线版本包含补充材料，可通过10.1186/s12883-022-02951-4获得。
Variants in the valosin-containing protein (VCP) gene were identified as one of the causes for inclusion body myopathy associated with Paget disease of the bone and frontotemporal dementia (FTD). Previously identified pathogenic variants in VCP are associated with frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) pathologically, but p.Asp395Gly VCP was recently reported to cause familial FTD with tauopathy characterized by neurofibrillary tau tangles (NFT) and not FTLD-TDP. We describe the clinical and genetic findings of a patient with p.Asp395Gly valosin-containing protein (VCP), who was diagnosed with FTD without a family history and in the absence of muscle or bone disease comorbidity. The patient was a 62-year-old man, who developed atypical depression at the age of 37 years. Subsequently, he presented with self-centered behavior at the age of 45 years. The self-centered behavior intensified from around the age of 50 years, which was accompanied by the development of executive dysfunction; therefore, he visited our hospital at 52 years of age. Magnetic resonance imaging revealed bilateral frontal lobe atrophy. Brain perfusion single-photon emission computed tomography revealed bilateral frontal lobe hypoperfusion. The patient fulfilled the diagnostic criteria for behavioral variant of FTD. Ten years after the diagnosis, computed tomography of the trunk and limbs, muscle biopsy, and bone scintigraphy revealed the absence of concomitant muscle and bone disease. The concentrations of cerebrospinal fluid (CSF) total tau and phosphorylated tau proteins were 389 pg/mL and 53.2 pg/mL (cut-off: 50 pg/mL), respectively. Genetic analyses were performed using the whole-exome and Sanger sequencing methods. We identified p.Asp395Gly VCP in this patient with pure FTD. p.Asp395Gly VCP was identified in a patient with likely sporadic FTD without concomitant muscle and bone disease. The CSF analysis suggested that our patient may have FTD due to NFT accumulation similar to the familial FTD patients with p.Asp395Gly VCP recently reported. Our findings suggest that a genetic search for the pathogenic variants of VCP should be considered not only for familial FTD, but also for patients with sporadic FTD, even in the absence of comorbid muscle or bone disease. The online version contains supplementary material available at 10.1186/s12883-022-02951-4.
登录
查看更多内容
影响因子：
5.1
作者：
Spina S;Van Laar AD;Murrell JR;Hamilton RL;Kofler JK;Epperson F;Farlow MR;Lopez OL;Quinlan J;DeKosky ST;Ghetti B
通讯作者：
Ghetti B
DOI：
10.1016/s1474-4422(12)70043-1
发表时间：
2012-04
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Majounie E;Renton AE;Mok K;Dopper EG;Waite A;Rollinson S;Chiò A;Restagno G;Nicolaou N;Simon-Sanchez J;van Swieten JC;Abramzon Y;Johnson JO;Sendtner M;Pamphlett R;Orrell RW;Mead S;Sidle KC;Houlden H;Rohrer JD;Morrison KE;Pall H;Talbot K;Ansorge O;Chromosome 9-ALS/FTD Consortium;French research network on FTLD/FTLD/ALS;ITALSGEN Consortium;Hernandez DG;Arepalli S;Sabatelli M;Mora G;Corbo M;Giannini F;Calvo A;Englund E;Borghero G;Floris GL;Remes AM;Laaksovirta H;McCluskey L;Trojanowski JQ;Van Deerlin VM;Schellenberg GD;Nalls MA;Drory VE;Lu CS;Yeh TH;Ishiura H;Takahashi Y;Tsuji S;Le Ber I;Brice A;Drepper C;Williams N;Kirby J;Shaw P;Hardy J;Tienari PJ;Heutink P;Morris HR;Pickering-Brown S;Traynor BJ
通讯作者：
Traynor BJ
影响因子：
3.5
作者：
Al-Obeidi E;Al-Tahan S;Surampalli A;Goyal N;Wang AK;Hermann A;Omizo M;Smith C;Mozaffar T;Kimonis V
通讯作者：
Kimonis V
影响因子：
3.7
作者：
Ikenaga C;Findlay AR;Seiffert M;Peck A;Peck N;Johnson NE;Statland JM;Weihl CC
通讯作者：
Weihl CC
影响因子：
4.4
作者：
Abrahao, Agessandro;Neto, Osorio Abath;Pedroso, Jose Luiz
通讯作者：
Pedroso, Jose Luiz