摘要
目的探讨1例癫痫患者的遗传学病因,并为其提供遗传咨询。方法选取2020年11月11日因有生育需求来山东大学附属生殖医院就诊的1例癫痫患者作为研究对象,收集患者的病史,通过全外显子组测序(WES)筛选候选变异,并进行Sanger测序验证。通过反转录-PCR及Sanger测序确定候选变异的致病性。结果患者为35岁女性,发病时无发热,意识丧失且颞叶出现异常放电,以抽搐、昏厥为主。WES检测显示其SCN9A基因存在c.2841+5G>A杂合变异,Sanger测序验证该位点。cDNA序列分析表明该变异导致SCN9A基因第16和17外显子之间插入了154个碱基,导致蛋白质翻译提前终止,产生截短蛋白,影响SCN9A蛋白的正常功能。根据美国医学遗传学与基因组学学会相关指南,判定为可能致病性变异(PVS1_Strong+PM2_Supporting)。结论SCN9A基因c.2841+5G>A变异可能是患者的遗传学病因。上述发现丰富了SCN9A基因的变异谱,同时为患者的产前诊断和胚胎植入前遗传学检测奠定了基础。
Objective To explore the genetic etiology of a patient with epilepsy and provide genetic counseling.Methods A patient who had visited the Center for Reproductive Medicine of Shandong University on November 11,2020 was selected as the study subject,and her clinic information was collected.Candidate variant was identified through whole exome sequencing(WES),and Sanger sequencing was used for validation.Possible transcriptional changes caused by the variant was detected by reverse transcription-PCR and Sanger sequencing.Results The patient was a 35-year-old female with no fever at the onset,loss of consciousness and abnormal firing in the temporal lobe,manifesting predominantly as convulsions and fainting.WES revealed that she had harbored a heterozygous c.2841+5G>A variant of the SCN9A gene,which was verified by Sanger sequencing.cDNA sequencing confirmed that 154 bases were inserted between exons 16 and 17 of the SCN9A gene,which probably produced a truncated protein and affected the normal function of the SCN9A protein.Based on the guidelines from the American College of Medical Genetics and Genomics,the c.2841+5G>A variant was classified as likely pathogenic(PVS1_Strong+PM2_Supporting).Conclusion The c.2841+5G>A variant of the SCN9A gene probably underlay the epilepsy in this patient.Above finding has enriched the variant spectrum of the SCN9A gene and provided a basis for the prenatal diagnosis and preimplantation genetic testing for this patient.
作者
尹训强
牛玉萍
邹洋
高媛
Yin Xunqiang;Niu Yuping;Zou Yang;Gao Yuan(Center for Reproductive Medicine,Shandong University,Jinan,Shandong 250012,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2023年第3期344-348,共5页
Chinese Journal of Medical Genetics
基金
国家重点研发计划(2022YFC2703200、2021YFC2700604、2021YFC2700500)
国家自然科学基金(31988101)
山东省重点研发计划(2020ZLYS02)。
