PDF(Pubmed)
Abstract：
OBJECTIVE: Myotonia is a clinical sign typical of a group of skeletal muscle channelopathies, the non-dystrophic myotonias. These disorders are electrophysiologically characterized by altered membrane excitability, due to specific genetic variants in known causative genes (CLCN1 and SCN4A). Juvenile Myoclonic Epilepsy (JME) is an epileptic syndrome identified as idiopathic generalized epilepsy, its genetics is complex and still unclarified. The co-occurrence of these two phenotypes is rare and the causes likely have a genetic background. In this study, we have genetically investigated an Italian family in which co-segregates myotonia, JME, or abnormal EEG without seizures was observed.
METHODS: All six individuals of the family, 4 affected and 2 unaffected, were clinically evaluated; EMG and EEG examinations were performed. For genetic testing, Exome Sequencing was performed for the six family members and Sanger sequencing was used to confirm the candidate variant.
RESULTS: Four family members, the mother and three siblings, were affected by myotonia. Moreover, EEG recordings revealed interictal generalized sharp-wave discharges in all affected individuals, and two siblings were affected by JME. All four affected members share the same identified variant, c.644 T > C, p.Ile215Thr, in SCN4A gene. Variants that could account for the epileptic phenotype alone, separately from the myotonic one, were not identified.
CONCLUSIONS: These results provide supporting evidence that both myotonic and epileptic phenotypes could share a common genetic background, due to variants in SCN4A gene. SCN4A pathogenic variants, already known to be causative of myotonia, likely increase the susceptibility to epilepsy in our family.
CONCLUSIONS: This study analyzed all members of an Italian family, in which the mother and three siblings had myotonia and epilepsy. Genetic analysis allowed to identify a variant in the SCN4A gene, which appears to be the cause of both clinical signs in this family.
METHODS: All six individuals of the family, 4 affected and 2 unaffected, were clinically evaluated; EMG and EEG examinations were performed. For genetic testing, Exome Sequencing was performed for the six family members and Sanger sequencing was used to confirm the candidate variant.
RESULTS: Four family members, the mother and three siblings, were affected by myotonia. Moreover, EEG recordings revealed interictal generalized sharp-wave discharges in all affected individuals, and two siblings were affected by JME. All four affected members share the same identified variant, c.644 T > C, p.Ile215Thr, in SCN4A gene. Variants that could account for the epileptic phenotype alone, separately from the myotonic one, were not identified.
CONCLUSIONS: These results provide supporting evidence that both myotonic and epileptic phenotypes could share a common genetic background, due to variants in SCN4A gene. SCN4A pathogenic variants, already known to be causative of myotonia, likely increase the susceptibility to epilepsy in our family.
CONCLUSIONS: This study analyzed all members of an Italian family, in which the mother and three siblings had myotonia and epilepsy. Genetic analysis allowed to identify a variant in the SCN4A gene, which appears to be the cause of both clinical signs in this family.
摘要：
目的：肌张力障碍是一组典型的骨骼肌信道病的临床体征，非营养不良的肌张力障碍。这些疾病的电生理特征是膜兴奋性改变，由于已知致病基因（CLCN1和SCN4A）中的特定遗传变异。青少年肌阵挛性癫痫（JME）是一种癫痫综合征，被确定为特发性全身性癫痫，它的遗传学是复杂的，仍然不清楚。这两种表型的共同出现是罕见的，原因可能有遗传背景。在这项研究中,我们对一个意大利家庭进行了基因研究，JME,或异常脑电图无癫痫发作。
方法：家庭中的所有六个人，4个受影响，2个不受影响，进行临床评估；进行肌电图和脑电图检查。基因检测,对六个家族成员进行外显子组测序,并使用Sanger测序来确认候选变体。
结果：四个家庭成员，母亲和三个兄弟姐妹，受到肌强直的影响。此外，脑电图记录显示所有受影响的个体发生间期广泛性锐波放电，和两个兄弟姐妹受到JME的影响。所有四个受影响的成员共享相同的识别变体，c.644T>C，p.Ile215Thr,SCN4A基因。可以单独解释癫痫表型的变体，与肌强直性的分开，未被识别。
结论：这些结果提供了支持证据，表明强直性和癫痫表型可能具有共同的遗传背景，由于SCN4A基因的变异。SCN4A致病性变异，已经知道是肌强直的原因，可能会增加我们家庭对癫痫的易感性。
结论：这项研究分析了意大利家庭的所有成员，其中母亲和三个兄弟姐妹患有肌强直和癫痫。遗传分析允许鉴定SCN4A基因中的变体，这似乎是这个家族中两种临床症状的原因。
方法：家庭中的所有六个人，4个受影响，2个不受影响，进行临床评估；进行肌电图和脑电图检查。基因检测,对六个家族成员进行外显子组测序,并使用Sanger测序来确认候选变体。
结果：四个家庭成员，母亲和三个兄弟姐妹，受到肌强直的影响。此外，脑电图记录显示所有受影响的个体发生间期广泛性锐波放电，和两个兄弟姐妹受到JME的影响。所有四个受影响的成员共享相同的识别变体，c.644T>C，p.Ile215Thr,SCN4A基因。可以单独解释癫痫表型的变体，与肌强直性的分开，未被识别。
结论：这些结果提供了支持证据，表明强直性和癫痫表型可能具有共同的遗传背景，由于SCN4A基因的变异。SCN4A致病性变异，已经知道是肌强直的原因，可能会增加我们家庭对癫痫的易感性。
结论：这项研究分析了意大利家庭的所有成员，其中母亲和三个兄弟姐妹患有肌强直和癫痫。遗传分析允许鉴定SCN4A基因中的变体，这似乎是这个家族中两种临床症状的原因。
