Abstract：
OBJECTIVE: To explore the genetic basis for a child featuring global developmental delay and epilepsy.
METHODS: A child who had presented at Guangzhou Women and Children\'s Medical Center Liuzhou Hospital on February 19, 2023 was selected as the study subject. Clinical data of the child was collected. The child was subjected to whole exome sequencing, and candidate variant was validated by Sanger sequencing and bioinformatic analysis.
RESULTS: The child, an 8-month-old girl, had manifested with global developmental delay, epilepsy, and hyperlactacidemia. Cranial MRI revealed diverse hypomyelinating leukodystrophies. Electroencephalogram showed slow background activities. Genetic testing revealed that she has harbored a homozygous variant of the SLC25A12 gene, namely c.115T>G (p.Phe39Val), for which both of her parents were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be of uncertain significance (PM2_Supporting+PM3_Supporting+PP3_Moderate+PP4_Moderate). I-Mutant v3.0 software predicted that the variant may affect the stability of protein product.
CONCLUSIONS: The homozygous c.115T>G (p.Phe39Val) variant of the SLC25A12 gene probably underlay the pathogenesis of the disease in this child.
METHODS: A child who had presented at Guangzhou Women and Children\'s Medical Center Liuzhou Hospital on February 19, 2023 was selected as the study subject. Clinical data of the child was collected. The child was subjected to whole exome sequencing, and candidate variant was validated by Sanger sequencing and bioinformatic analysis.
RESULTS: The child, an 8-month-old girl, had manifested with global developmental delay, epilepsy, and hyperlactacidemia. Cranial MRI revealed diverse hypomyelinating leukodystrophies. Electroencephalogram showed slow background activities. Genetic testing revealed that she has harbored a homozygous variant of the SLC25A12 gene, namely c.115T>G (p.Phe39Val), for which both of her parents were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be of uncertain significance (PM2_Supporting+PM3_Supporting+PP3_Moderate+PP4_Moderate). I-Mutant v3.0 software predicted that the variant may affect the stability of protein product.
CONCLUSIONS: The homozygous c.115T>G (p.Phe39Val) variant of the SLC25A12 gene probably underlay the pathogenesis of the disease in this child.
摘要：
目的：探索以全球发育迟缓和癫痫为特征的儿童的遗传基础。
方法：选择2023年2月19日在广州市妇女儿童医学中心柳州医院就诊的儿童作为研究对象。收集患儿的临床资料。这个孩子接受了整个外显子组测序，候选变异体通过Sanger测序和生物信息学分析进行验证。
结果：孩子，一个8个月大的女孩,表现为全球发育迟缓，癫痫,和高乳酸血症.颅骨MRI显示不同的骨髓增生性脑白质营养不良。脑电图显示背景活动缓慢。基因检测显示，她携带了SLC25A12基因的纯合变体，即c.115T>G(p.Phe39Val),她的父母都是杂合携带者。根据美国医学遗传学和基因组学学院的指南，预测该变体具有不确定的意义(PM2_支持+PM3_支持+PP3_中度+PP4_中度)。I-Mutantv3.0软件预测该变体可能会影响蛋白质产物的稳定性。
结论：纯合c.115T>G（p。Phe39Val）SLC25A12基因的变异可能是该儿童疾病的发病机理。
方法：选择2023年2月19日在广州市妇女儿童医学中心柳州医院就诊的儿童作为研究对象。收集患儿的临床资料。这个孩子接受了整个外显子组测序，候选变异体通过Sanger测序和生物信息学分析进行验证。
结果：孩子，一个8个月大的女孩,表现为全球发育迟缓，癫痫,和高乳酸血症.颅骨MRI显示不同的骨髓增生性脑白质营养不良。脑电图显示背景活动缓慢。基因检测显示，她携带了SLC25A12基因的纯合变体，即c.115T>G(p.Phe39Val),她的父母都是杂合携带者。根据美国医学遗传学和基因组学学院的指南，预测该变体具有不确定的意义(PM2_支持+PM3_支持+PP3_中度+PP4_中度)。I-Mutantv3.0软件预测该变体可能会影响蛋白质产物的稳定性。
结论：纯合c.115T>G（p。Phe39Val）SLC25A12基因的变异可能是该儿童疾病的发病机理。
