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Abstract：
Whole-exome sequencing (WES), one of the next-generation sequencing (NGS), has become a powerful tool to identify exonic variants. Investigating causality of the sequence variants in human disease becomes an important part in NGS for the research and clinical applications. Recently, important guidelines on them have been published and will keep on updating. In our study, two Chinese families, with the clinical diagnosis of \"Epilepsy\", which presented with seizures, psychomotor retardation, hypotonia and etc. features, were sequenced by Trio-WES (including the proband and the unaffected parents), and a standard interpretation of the identified variants was performed referring to the recently updated guidelines. Finally, we identified three novel mutations (c.71 C > T, p.P24L; c.1387-1389delGAG, p.E463-; c.134 G > A, p.W45*; NM_000026) in ADSL in the two Chinese families, and confirmed them as the causal variants to the disease-Adenylosuccinate Lyase Deficiency. Previous reported specific therapy was also introduced to the patients after our refined molecular diagnosis, however, the effect was very limited success. In summary, our study demonstrated the power and advantages of WES in exploring the etiology of human disease. Using the constantly updated guidelines to conduct the WES study and to interpret the sequence variants are a necessary strategy to make the molecular diagnosis and to guide the individualized treatment of human disease.
摘要：
全外显子组测序(WES),下一代测序（NGS）之一，已经成为识别外显子变体的强大工具。研究人类疾病中序列变异的因果关系成为NGS研究和临床应用的重要组成部分。最近,有关它们的重要准则已经发布，并将不断更新。在我们的研究中,两个中国家庭,临床诊断为“癫痫”，出现癫痫发作，精神运动性迟钝,肌张力减退等.特点,由Trio-WES（包括先证者和未受影响的父母）测序，并参考最近更新的指南对鉴定的变异进行标准解释.最后,我们确定了三个新的突变(c.71C>T，p.P24L;c.1387-1389delGAG,p.E463-;c.134G>A,p.W45*;NM_000026)在两个中国家庭的ADSL中，并证实它们是琥珀酸腺苷酸裂解酶缺乏症的因果变异。先前报道的特异性治疗也被引入到我们的精细分子诊断后的患者，然而,效果非常有限。总之,我们的研究证明了WES在探索人类疾病病因方面的力量和优势。使用不断更新的指南进行WES研究并解释序列变异是进行分子诊断和指导人类疾病个体化治疗的必要策略。
