Yang Zhigang, Wang Yuan, Chen Guohong, Song Lifang, Ma Yanli, Zhang Weihua
Department of Neurology, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450066, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2024 Mar 10;41(3):284-288. doi: 10.3760/cma.j.cn511374-20221102-00752.
To analyze the clinical and genetic characteristics of three Chinese pedigrees affected with Genetic epilepsy with febrile seizures plus (GEFS+).
Three GEFS+ probands and their pedigree members presented at the Children's Hospital of Zhengzhou University from January 2020 to December 2021 were selected as the study subjects. Clinical data of the pedigrees were collected. Whole exome sequencing was carried out for the probands, and Sanger sequencing was used to verify the candidate variants.
Proband 1 was a 3-year-and-2-month-old male with febrile seizure plus. His father, two aunts, grandmother, aunt grandmother, uncle grandfather, and paternal great-grandmother also had onset of febrile seizures at 1 ~ 2 years of age with remission before 6 years old. Proband 2 was a 1-year-and-4-month-old male with complex febrile seizure. His mother, maternal uncle, and maternal grandmother also had febrile seizures before 5 ~ 6 years of age. Proband 3 was a 3-year-and-11-month-old male with febrile seizure plus. His father and grandfather also had febrile seizures plus with remission at 7 ~ 8 years of age. Genetic testing revealed that proband 1 had harbored a paternally derived heterozygous SCN1A: c.1613T>C variant, proband 2 had harbored a maternally derived heterozygous SCN1A: c.2804A>G variant, and proband 3 had harbored a paternally derived heterozygous SCN1A: c.1271T>C variant. All of the three variants were predicted as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (PM1+PM2_Supporting+PP1+PP3+PP4).
The c.1613T>C, c.2804A>G and c.1271T>C variants probably underlay the pathogenesis of GEFS+ in these pedigrees.
分析三个中国遗传性热性惊厥附加症（GEFS+）家系的临床和遗传特征。
选取2020年1月至2021年12月在郑州大学儿童医院就诊的三名GEFS+先证者及其家系成员作为研究对象。收集家系的临床资料。对先证者进行全外显子组测序，并采用桑格测序法验证候选变异。
先证者1为一名3岁2个月大的男性，患有热性惊厥附加症。他的父亲、两位姑姑、祖母、姑祖母、叔祖父和父系曾祖母在1至2岁时也有热性惊厥发作，6岁前缓解。先证者2为一名1岁4个月大的男性，患有复杂性热性惊厥。他的母亲、舅舅和外祖母在5至6岁前也有热性惊厥发作。先证者3为一名3岁11个月大的男性，患有热性惊厥附加症。他的父亲和祖父也有热性惊厥附加症，7至8岁时缓解。基因检测显示，先证者1携带父源杂合的SCN1A:c.1613T>C变异，先证者2携带母源杂合的SCN1A:c.2804A>G变异，先证者3携带父源杂合的SCN1A:c.1271T>C变异。根据美国医学遗传学与基因组学学会的指南（PM1+PM2_Supporting+PP1+PP3+PP4），这三个变异均被预测为可能致病。
c.1613T>C、c.2804A>G和c.1271T>C变异可能是这些家系中GEFS+发病机制的基础。
