SLC13A5 Deficiency Disorder: From Genetics to Gene Therapy.
SLC13A5 Deficiency Disorder: From Genetics to Gene Therapy.
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作者：
癫痫性脑病可能由单基因变异引起。近年来，下一代测序技术使单基因癫痫的基因鉴定出现了爆炸式增长。其中一个例子是癫痫性脑病SLC13A5缺乏性障碍，这是由SLC13A5基因的功能致病性变异丧失引起的，导致钠/柠檬酸共转运体缺乏。患者通常在生命的第一周内经历癫痫发作，并有发育迟缓和智力残疾。目前的抗癫痫药物可能会降低癫痫发作频率，但需要更有针对性的治疗来解决SLC13A5缺乏症的癫痫性和非癫痫性特征。基因治疗可能给这些患者带来希望，并且比现有的治疗方法有更好的临床效果。在这里，我们讨论了SLC13A5的遗传、自然历史、可用的治疗方法、潜在的结果和评估，以及基于aav9基因替代疗法的转化医学研究的考虑。
Epileptic encephalopathies may arise from single gene variants. In recent years, next-generation sequencing technologies have enabled an explosion of gene identification in monogenic epilepsies. One such example is the epileptic encephalopathy SLC13A5 deficiency disorder, which is caused by loss of function pathogenic variants to the gene SLC13A5 that results in deficiency of the sodium/citrate cotransporter. Patients typically experience seizure onset within the first week of life and have developmental delay and intellectual disability. Current antiseizure medications may reduce seizure frequency, yet more targeted treatments are needed to address the epileptic and non-epileptic features of SLC13A5 deficiency disorder. Gene therapy may offer hope to these patients and better clinical outcomes than current available treatments. Here, we discuss SLC13A5 genetics, natural history, available treatments, potential outcomes and assessments, and considerations for translational medical research for an AAV9-based gene replacement therapy.
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DOI：
10.3390/molecules22030378
发表时间：
2017-02-28
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Bhutia YD;Kopel JJ;Lawrence JJ;Neugebauer V;Ganapathy V
通讯作者：
Ganapathy V
影响因子：
3.7
作者：
Irizarry AR;Yan G;Zeng Q;Lucchesi J;Hamang MJ;Ma YL;Rong JX
通讯作者：
Rong JX
影响因子：
2
作者：
Arvio, Maria;Lahdetie, Jaana
通讯作者：
Lahdetie, Jaana
影响因子：
4.1
作者：
FANG, M;LOWENSTEIN, JM
通讯作者：
LOWENSTEIN, JM
影响因子：
4.1
作者：
Inoue, K;Fei, YJ;Ganapathy, V
通讯作者：
Ganapathy, V