Biallelic DDHD2 mutations in patients with adult-onset complex hereditary spastic paraplegia.
Biallelic DDHD2 mutations in patients with adult-onset complex hereditary spastic paraplegia.
复制标题
DOI：
10.1002/acn3.51850
复制
发表时间：
2023-09
影响因子：
5.3
通讯作者：
Lee, Yi-Chung
中科院分区：
文献类型：
--
作者：
Chou, Ying-Tsen;Hsu, Shao-Lun;Tsai, Yu-Shuen;Lu, Yi-Jiun;Yu, Kai-Wei;Wu, Hsiu-Mei;Liao, Yi-Chu;Lee, Yi-Chung
遗传性痉挛性截瘫是一组以缓慢进行性下肢痉挛和无力为特征的遗传性神经退行性疾病。HSP 54型（SPG 54）是由DDHD 2基因突变引起的常染色体隐性遗传。本研究调查了一组台湾HSP患者的临床特征和DDHD 2突变的分子特征。对242例无血缘关系的台湾HSP患者进行DDHD 2突变分析。双等位基因DDHD 2突变患者的临床，神经影像学和遗传特征进行了表征。进行基于细胞的研究以评估DDHD 2突变对蛋白质表达的影响。SPG 54在3例患者中被诊断。其中，2例患者携带复合杂合子DDHD 2突变，p. [R112 Q];[Y 606 *]和p. [R112 Q];[p.D660H]，另一个是DDHD 2 p.R112Q突变纯合子。DDHD 2 p.Y606* 是一种新的突变，而DDHD 2 p.D660H和p.R112Q已在文献中报道。这三名患者均表现为成人发作的复杂HSP，并伴有小脑共济失调、多发性神经病或认知障碍。脑质子磁共振波谱显示，异常的脂质峰在丘脑的所有三名患者。体外研究表明，所有三种DDHD 2突变均与相当低的DDHD 2蛋白水平相关。SPG 54在约1.2%（3/242）的台湾HSP队列中检测到。这项研究扩展了DDHD 2的已知突变谱，提供了DDHD 2突变致病性的分子证据，并强调了将SPG 54视为成人发病HSP的潜在诊断的重要性。
Hereditary spastic paraplegias (HSPs) are a group of inherited neurodegenerative disorders characterized by slowly progressive lower limb spasticity and weakness. HSP type 54 (SPG54) is autosomal recessively inherited and caused by mutations in the DDHD2 gene. This study investigated the clinical characteristics and molecular features of DDHD2 mutations in a cohort of Taiwanese patients with HSP. Mutational analysis of DDHD2 was performed for 242 unrelated Taiwanese patients with HSP. The clinical, neuroimaging, and genetic features of the patients with biallelic DDHD2 mutations were characterized. A cell‐based study was performed to assess the effects of the DDHD2 mutations on protein expression. SPG54 was diagnosed in three patients. Among them, two patients carried compound heterozygous DDHD2 mutations, p.[R112Q];[Y606*] and p.[R112Q];[p.D660H], and the other one was homozygous for the DDHD2 p.R112Q mutation. DDHD2 p.Y606* is a novel mutation, whereas DDHD2 p.D660H and p.R112Q have been reported in the literature. All three patients manifested adult onset complex HSP with additional cerebellar ataxia, polyneuropathy, or cognitive impairment. Brain proton magnetic resonance spectroscopy revealed an abnormal lipid peak in thalamus of all three patients. In vitro studies demonstrated that all the three DDHD2 mutations were associated with a considerably lower DDHD2 protein level. SPG54 was detected in approximately 1.2% (3 of 242) of the Taiwanese HSP cohort. This study expands the known mutational spectrum of DDHD2, provides molecular evidence of the pathogenicity of the DDHD2 mutations, and underlines the importance of considering SPG54 as a potential diagnosis of adult‐onset HSP.
登录
查看更多内容
影响因子：
6
作者：
Nicita, Francesco;Stregapede, Fabrizia;Travaglini, Lorena
通讯作者：
Travaglini, Lorena
影响因子：
3.3
作者：
Koh K;Ishiura H;Tsuji S;Takiyama Y
通讯作者：
Takiyama Y
DOI：
10.1073/pnas.1413706111
发表时间：
2014-10-14
影响因子：
11.1
作者：
Inloes, Jordon M.;Hsu, Ku-Lung;Cravatt, Benjamin F.
通讯作者：
Cravatt, Benjamin F.
影响因子：
3.5
作者：
Sato, Sei-ichi;Inoue, Hiroki;Tani, Katsuko
通讯作者：
Tani, Katsuko
影响因子：
2.6
作者：
Xu, Xin;Lu, Fen;Du, Senjie;Zhao, Xiaoke;Li, Hongying;Zhang, Li;Tang, Jian
通讯作者：
Tang, Jian