目的 探讨1例表现为癫痫、感音神经性耳聋、共济失调、智力障碍的男性EAST/SeSAME患儿的遗传学病因。 方法 选取2021年1月至郑州大学第三附属医院就诊的1例EAST/SeSAME综合征患儿为研究对象。对患儿及其父母进行高通量测序检测，对候选变异进行Sanger测序验证及生物信息学分析。 结果 测序结果显示患儿KCNJ10基因存在c.557T>C(p.Val186Ala)和c.386T>A(p.Ile129Asn)复合杂合变异，Sanger测序证实二者分别遗传自其母亲和父亲。根据美国医学遗传学与基因组学学会(ACMG)相关指南，二者均判定为可能致病性变异(PM1+PM2_Supporting+PP3+PP4 PM1+PM2_Supporting+PM3+PP3+PP4)。 结论 患者为KCNJ10基因复合杂合变异所致的EAST/SeSAME综合征。上述发现丰富了KCNJ10基因的变异谱，并为患儿家庭的遗传咨询及产前诊断提供了依据。 Objective To explore the genetic basis for a EAST/SeSAME child featuring epilepsy, ataxia, sensorineural deafness and intellectual disability. Methods A child with EAST/SeSAME syndrome who presented the Third Affiliated Hospital of Zhengzhou University in January 2021 was selected as the study object. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. Results Genetic testing revealed that the child has harbored compound heterozygous variants of the KCNJ10 gene, namely c. 557T>C (p.Val186Ala) and c. 386T>A (p.Ile129Asn), which were inherited from her mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted as likely pathogenic(PM1+ PM2_Supporting+ PP3+ PP4 PM1+ PM2_Supporting+ PM3+ PP3+ PP4). Conclusion The patient was diagnosed with EAST/SeSAME syndrome due to the compound heterozygous variants of the KCNJ10 gene.
Abstract
Objective To explore the genetic basis for a EAST/SeSAME child featuring epilepsy, ataxia, sensorineural deafness and intellectual disability. Methods A child with EAST/SeSAME syndrome who presented the Third Affiliated Hospital of Zhengzhou University in January 2021 was selected as the study object. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. Results Genetic testing revealed that the child has harbored compound heterozygous variants of the KCNJ10 gene, namely c. 557T>C (p.Val186Ala) and c. 386T>A (p.Ile129Asn), which were inherited from her mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted as likely pathogenic(PM1+ PM2_Supporting+ PP3+ PP4 PM1+ PM2_Supporting+ PM3+ PP3+ PP4). Conclusion The patient was diagnosed with EAST/SeSAME syndrome due to the compound heterozygous variants of the KCNJ10 gene.
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