Department of Neurology, Soochow University Affiliated Children's Hospital, Suzhou, Jiangsu, China.
J Mol Neurosci. 2021 Sep;71(9):1944-1950. doi: 10.1007/s12031-021-01880-0. Epub 2021 Jul 4.
Progressive myoclonic epilepsy is a group of neurodegenerative diseases with complex clinical and genetic heterogeneity, which is associated with spontaneous or action-induced myoclonus and progressive neurodegeneration. Since 2020, 4 families with progressive myoclonic epilepsy-11 [OMIM#618876] have been reported with a very limited spectrum of SEMA6B pathogenic variants. In our study, whole-exome sequencing was used in a proband from a nonconsanguineous Chinese family presenting with growth retardation and recurrent atonic seizures. A deletion mutation (c.1960_1978del, p.Leu654Argfs*25) in the last exon of SEMA6B was detected, which is a de novo variant and pathogenic. The new genetic evidence we reported here strengthened the gene-disease relationship, and the gene curation level between SEMA6B and progressive myoclonic epilepsy-11 became "strong" following the ClinGen SOP. Therefore, the results of this study broaden the mutation spectrum of SEMA6B in different ethnic groups and strengthen the gene-disease relationship between SEMA6B and progressive myoclonic epilepsy-11.
进行性肌阵挛癫痫是一组具有复杂临床和遗传异质性的神经退行性疾病，其与自发性或动作诱发的肌阵挛和进行性神经退行性变有关。自 2020 年以来，已经报道了 4 个具有进行性肌阵挛癫痫-11[OMIM#618876]的家族，这些家族的 SEMA6B 致病变体谱非常有限。在我们的研究中，使用全外显子组测序对来自一个非近亲结婚的中国家庭的先证者进行了研究，该先证者表现为生长迟缓和复发性失神发作。在 SEMA6B 的最后一个外显子中检测到缺失突变（c.1960_1978del，p.Leu654Argfs*25），这是一个新生变异和致病性变异。我们在这里报告的新遗传证据加强了基因-疾病的关系，并且根据 ClinGen SOP，SEMA6B 和进行性肌阵挛癫痫-11 之间的基因校正水平变为“强”。因此，这项研究拓宽了不同人群中 SEMA6B 的突变谱，并加强了 SEMA6B 与进行性肌阵挛癫痫-11 之间的基因-疾病关系。
