Identification of a Novel Homozygous Splice-Site Mutation in SCARB2 that Causes Progressive Myoclonus Epilepsy with or without Renal Failure.
Identification of a Novel Homozygous Splice-Site Mutation in SCARB2 that Causes Progressive Myoclonus Epilepsy with or without Renal Failure.
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鉴定 SCARB2 中新型纯合剪接位点突变，该突变可导致进行性肌阵挛癫痫伴或不伴肾功能衰竭。
DOI：
10.4103/0366-6999.235113
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发表时间：
2018-07-05
影响因子：
6.1
通讯作者：
Chen WJ
中科院分区：
文献类型：
--
作者：
He J;Lin H;Li JJ;Su HZ;Wang DN;Lin Y;Wang N;Chen WJ
进行性肌阵挛性癫痫（PMEs）是一组罕见的遗传性疾病，其特征是肌阵挛、癫痫发作和共济失调伴进行性神经功能下降。由于PME的临床和遗传异质性，很难确定哪些基因受到影响。本研究的目的是报告一个动作性肌阵挛伴或不伴肾功能衰竭综合征（EPM 4）家系，并总结所有报告的EPM 4患者的临床和遗传特征。本研究应用靶向下一代测序技术（NGS）对一个中国PME家系的致病基因进行了筛选。通过共分离分析和进一步的功能分析，包括先证者肌肉的逆转录聚合酶链反应和Western blot，进一步证实候选变异体。此外，对所有报告的EPM 4患者的临床和突变特征的文献数据进行了审查。基因分析揭示了一个新的纯合剪接突变（c.995-1G>A）的SCARB 2基因在两个兄弟。进一步的功能分析显示，该突变导致SCARB 2蛋白功能丧失。根据美国医学遗传学和基因组学学会的标准和指南以及功能分析，候选变体的分类是致病性的。因此，这两兄弟最终被确诊为EPM 4。这些目前的结果表明，有针对性的NGS进行更快速，更准确的诊断PME患者的潜力。文献综述显示SCARB 2不同功能域的突变似乎与EPM 4的表型相关。
Progressive myoclonus epilepsies (PMEs) comprise a group of rare genetic disorders characterized by action myoclonus, epileptic seizures, and ataxia with progressive neurologic decline. Due to clinical and genetic heterogeneity of PMEs, it is difficult to decide which genes are affected. The aim of this study was to report an action myoclonus with or without renal failure syndrome (EPM4) family and summarize the clinical and genetic characteristics of all reported EPM4 patients. In the present study, targeted next-generation sequencing (NGS) was applied to screen causative genes in a Chinese PME family. The candidate variant was further confirmed by cosegregation analysis and further functional analysis, including the reverse transcription polymerase chain reaction and Western blot of the proband's muscle. Moreover, literature data on the clinical and mutational features of all reported EPM4 patients were reviewed. The gene analysis revealed a novel homozygous splicing mutation (c.995-1G>A) of the SCARB2 gene in two brothers. Further functional analysis revealed that this mutation led to loss function of the SCARB2 protein. The classification of the candidate variant, according to the American College of Medical Genetics and Genomics standards and guidelines and functional analysis, was pathogenic. Therefore, these two brothers were finally diagnostically confirmed as EPM4. These present results suggest the potential for targeted NGS to conduct a more rapid and precise diagnosis for PME patients. A literature review revealed that mutations in the different functional domains of SCARB2 appear to be associated with the phenotype of EPM4.
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影响因子：
4.5
作者：
Do CB;Tung JY;Dorfman E;Kiefer AK;Drabant EM;Francke U;Mountain JL;Goldman SM;Tanner CM;Langston JW;Wojcicki A;Eriksson N
通讯作者：
Eriksson N
影响因子：
8.6
作者：
Michelakakis, Helen;Xiromerisiou, Georgia;Hadjigeorgiou, Georgios M.
通讯作者：
Hadjigeorgiou, Georgios M.
影响因子：
4
作者：
Kousi M;Anttila V;Schulz A;Calafato S;Jakkula E;Riesch E;Myllykangas L;Kalimo H;Topçu M;Gökben S;Alehan F;Lemke JR;Alber M;Palotie A;Kopra O;Lehesjoki AE
通讯作者：
Lehesjoki AE
影响因子：
3.5
作者：
Damiano, John A.;Afawi, Zaid;Hildebrand, Michael S.
通讯作者：
Hildebrand, Michael S.
影响因子：
5.2
作者：
Gómez-Garre, P;Sanz, Y;Serratosa, JM
通讯作者：
Serratosa, JM